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Peptic ulcer

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Peptic ulcer

  1. 1. PEPTIC ULCERPEPTIC ULCER
  2. 2. DefinitionsDefinitions Ulcer:Ulcer: A lesion on an epithelial surface (skin or mucousA 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”
  3. 3. What is Peptic Ulcer ?What is Peptic Ulcer ? A peptic ulcer disease or PUD is an ulcer (defined as mucosalA peptic ulcer disease or PUD is an ulcer (defined as mucosal erosions equal to or greater than 0.5 cm) of an area of theerosions 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 toGastritis 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 DiverticulumMeckel's Diverticulum (called Meckel's Diverticulum ulcer)ulcer)
  4. 4. Peptic Ulcer DiseasePeptic Ulcer Disease
  5. 5. Gastric Mucosa & SecretionsGastric Mucosa & Secretions The inside of the stomach is bathed in about 2 liters ofThe 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 tearconcentrated 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
  6. 6. Gastric Mucosa & SecretionsGastric Mucosa & Secretions The Defensive Forces Bicarbonate Mucus layer Mucosal blood flow Prostaglandins Growth factors The Aggressive Forces Helicobacter pylori HCl acid Pepsins NSAIDs Bile acids Ischemia and hypoxia. Smoking and alcohol When the aggressive factors increase or the defensive factors decrease, mucosal damage will result, leading to erosions & ulcerations
  7. 7. Because of ImbalanceBecause of Imbalance Imbalance primarily between Aggressive factorsImbalance 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
  8. 8. Phases of gastric secretionPhases of gastric secretion Phase 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
  9. 9. Gastric secretionsGastric secretions 1.1. PepsinogensPepsinogens (Chief cells).(Chief cells). 2.2. HCl and intrinsic factorHCl and intrinsic factor (Parietal cells).(Parietal cells). 3.3. GastrinGastrin (G-cells).(G-cells). 4.4. Mucus, bicarbonateMucus, bicarbonate (mucus-secreting cells).(mucus-secreting cells).
  10. 10. Regulation of Gastric secretionsRegulation of Gastric secretions 1.1. HistamineHistamine (local hormone)(local hormone) 2.2. AcetylcholineAcetylcholine (neurotransmitter).(neurotransmitter). 3.3. GastrinGastrin (hormone).(hormone).
  11. 11. ProglumideACh PGE2 Histamine Gastrin Adenyl cyclase _ + ATP cAMP Protein Kinase (Activated) Ca++ + Ca++ Proton pump KK+ H+ Gastric acid Parietal cell Lumen of stomach Antacid Omeprazole Ranitidine H2M3 Misoprostol _ _ _ _ + PGE receptor + + Gastrin receptor+ + +
  12. 12. Illustration of Gastric secretion by parietal cells
  13. 13. What may contributeWhat may contribute imbalance ?imbalance ? Helicobacter pyloriHelicobacter pylori NSAIDsNSAIDs EthanolEthanol TobaccoTobacco Severe physiologicSevere physiologic stress (Burns, CNS trauma,stress (Burns, CNS trauma, Surgery, Severe medical illness)Surgery, Severe medical illness) SteroidsSteroids
  14. 14. 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
  15. 15. 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 infections Vascular insufficiencyVascular insufficiency
  16. 16. ETIOLOGIC FACTORS OF PUD
  17. 17. 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
  18. 18. EtiologyEtiology  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)
  19. 19. 1. Etiology –1. Etiology – Helicobacter pyloriHelicobacter pylori
  20. 20. H.pyloriH.pylori EpidemiologyEpidemiology One half of worldOne half of world’’s population hass population has H.pyloriH.pylori infection, withinfection, with an estimated prevalence of 80-90 % in the developingan estimated prevalence of 80-90 % in the developing worldworld The annual incidence of newThe annual incidence of new H. pyloriH. pylori infections ininfections in industrialized countries is 0.5% of the susceptibleindustrialized countries is 0.5% of the susceptible population compared with ≥ 3% in developing countriespopulation compared with ≥ 3% in developing countries
  21. 21. H.pyloriH.pylori as a cause of PUDas a cause of PUD
  22. 22. H.pyloriH.pylori as a cause of PUDas a cause of PUD DU GU 95%85%
  23. 23. Pathogenesis ofPathogenesis of H. pyloriH. pylori infectioninfection 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-personTransmitted from person-to-person by Oro–oral or feco-oral spreadby Oro–oral or feco-oral spread No reservoir in animal or waterNo reservoir in animal or water supplysupply
  24. 24. Dynamics of H.pylori infectionDynamics of H.pylori infection Dr.T.V.Rao MDDr.T.V.Rao MD 2626
  25. 25. Urease C=O(NH2)2 + H+ + 2H2O  HCO3 - + 2 (NH4 + ) Urea Bicarbonate Ammonium ions And then… HCO3 -  CO2 + OH- Urea Hydrolysis
  26. 26. Pathogenesis ofPathogenesis of H. pyloriH. pylori infectioninfection The Flagellae make it motile,The Flagellae make it motile, allowing it to live deep beneathallowing it to live deep beneath the mucus layerthe mucus layer It uses an adhesin molecule toIt uses an adhesin molecule to bind to epithelial cells Where thebind to epithelial cells Where the pH there is close to neutralpH there is close to neutral
  27. 27. Pathogenesis ofPathogenesis of H. pyloriH. pylori infectioninfection Any acidity is buffered by theAny acidity is buffered by the organism's production of theorganism's production of the enzyme urease, which catalyzesenzyme urease, which catalyzes the production of ammonia (NH3)the production of ammonia (NH3) from urea & raises the pH therefrom urea & raises the pH there The bacterium stimulates chronicThe bacterium stimulates chronic gastritis by provoking a localgastritis by provoking a local inflammatory response.inflammatory response.
  28. 28. Pathogenesis ofPathogenesis of H. pyloriH. pylori infectioninfection In the cellular level:In the cellular level: H. pyloriH. pylori expressexpress cagAcagA && vacAvacA genesgenes cagAcagA genegene  signals to thesignals to the epithelial cells involving:epithelial cells involving: - Cell replication,- Cell replication, - Apoptosis, &- Apoptosis, & - Morphology- Morphology
  29. 29. Pathogenesis ofPathogenesis of H. pyloriH. pylori infectioninfection In the cellular level:In the cellular level: vacAvacA genegene  producingproducing a pore-forming protein, whicha pore-forming protein, which has many destructing effect tohas 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 cellSuppression of local cell immunityimmunity
  30. 30. Pathogenesis ofPathogenesis of H. pyloriH. pylori infectioninfection - ↓ 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!
  31. 31. Carcinogenic effect ofCarcinogenic effect of H. pyloriH. pylori H. pylori Host Factors Other environmental Factors Antral gastritis Pangastritis DU GU Gastritis Cancer
  32. 32. Carcinogenic effect ofCarcinogenic effect of H. pyloriH. pylori Epidemiologic evidence suggests that infection with HP isEpidemiologic 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 HPHowever due to uncertainty regarding the benefit of HP eradication on reducing cancer risk, wide-spread screeningeradication on reducing cancer risk, wide-spread screening for HP in asymptomatic individuals cannot befor HP in asymptomatic individuals cannot be recommended at this timerecommended at this time
  33. 33. 2. Etiology -Non-Steroidal Anti-inflammatory2. Etiology -Non-Steroidal Anti-inflammatory Drugs (NSAIDS)Drugs (NSAIDS)
  34. 34. NSAIDSNSAIDS Symptomatic GI ulceration occurs in 2% - 4% of patientsSymptomatic 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 ofthese small percentages translate into a large number of symptomatic ulcerssymptomatic ulcers The effects of aspirin & NSAIDs on the gastric mucosa rangesThe effects of aspirin & NSAIDs on the gastric mucosa ranges from mucosal hemorrhages to erosions & acute ulcersfrom mucosal hemorrhages to erosions & acute ulcers
  35. 35. NSAIDSNSAIDS  Inhibits the production ofInhibits the production of prostaglandinsprostaglandins precursor fromprecursor from membrane fatty acids resulting in: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 & products ofThe drugs also generate oxygen-free radicals & products of the lipoxygenase pathway that may contribute to ulcerationthe lipoxygenase pathway that may contribute to ulceration
  36. 36. NSAIDSNSAIDS  Gastric acid probably aggravates NSAID-induce mucosalGastric acid probably aggravates NSAID-induce mucosal injury byinjury 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
  37. 37. NSAIDSNSAIDS Users of NSAIDs are at approximately 3 times greaterUsers of NSAIDs are at approximately 3 times greater relative risk of serious adverse gastrointestinal events thanrelative risk of serious adverse gastrointestinal events than nonusersnonusers
  38. 38. NSAIDSNSAIDS  Identify risk factors:Identify risk factors: Age > 65 years (3.5-fold increased risk)Age > 65 years (3.5-fold increased risk) SmokingSmoking Previous history of GI event (e.g. ulcer bleeding 4-fold increasePrevious history of GI event (e.g. ulcer bleeding 4-fold increase risk)risk) Concomitant drug useConcomitant 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)
  39. 39. 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
  40. 40. Psychological Stress UlcersPsychological Stress Ulcers Gastric mucosa of body of stomach undergoes a period ofGastric mucosa of body of stomach undergoes a period of transient ischemia in association withtransient ischemia in association with HypotensionHypotension Severe injurySevere injury Extensive burnsExtensive burns Complicated surgeryComplicated surgery
  41. 41. Psychological Stress UlcersPsychological Stress Ulcers Ischemia due to capillary blood flow or shunting of blood↓Ischemia due to capillary blood flow or shunting of blood↓ away from GI tract so that blood flow bypasses gastricaway from GI tract so that blood flow bypasses gastric mucosamucosa Imbalance between destructive properties of HCl acid andImbalance between destructive properties of HCl acid and pepsin, and protective factors of stomachpepsin, and protective factors of stomach’’s mucosal barriers mucosal barrier
  42. 42. Back-Diffusion of AcidsBack-Diffusion of Acids Fig. 40-13
  43. 43. Two major variants in peptic ulcers are commonlyTwo 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)
  44. 44. TypesTypes AcuteAcute Superficial erosionSuperficial erosion Minimal erosionMinimal erosion ChronicChronic Muscular wall erosion with formation of fibrous tissueMuscular wall erosion with formation of fibrous tissue Present continuously for many months or intermittentlyPresent continuously for many months or intermittently
  45. 45. RecurrenceRecurrence Risk factors for recurrence include:Risk factors for recurrence include: Non-ulcer dyspepsiaNon-ulcer dyspepsia Persistence of chronic gastritis after eradication therapyPersistence of chronic gastritis after eradication therapy Female genderFemale gender Intellectual disabilityIntellectual disability Younger ageYounger age High rates of primary infectionHigh rates of primary infection Higher urea breath test valuesHigher urea breath test values ABLES A Z et al. American Family Physician. 2007
  46. 46. Clinical PresentationClinical Presentation Recurrent 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 foodRelieved by food  DUDU Precipitated by foodPrecipitated 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 ofPain may be absent or less characteristic in one-third of patients especially in elderly patients on NSAIDspatients especially in elderly patients on NSAIDs
  47. 47. 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 gastrointestinalHematemesis or melena resulting from gastrointestinal bleedingbleeding Weight lossWeight loss
  48. 48. Duodenal Vs Gastric UlcersDuodenal Vs Gastric Ulcers DuodenalDuodenal Age: 25-75 yearsAge: 25-75 years Gnawing or burning upperGnawing or burning upper abdomen pain relieved by foodabdomen pain relieved by food but reappears 1-3 hrs after mealsbut reappears 1-3 hrs after meals Worse pain when stomach emptyWorse pain when stomach empty Bleeding occurs with deepBleeding occurs with deep erosionerosion HematemesisHematemesis MelenaMelena GastricGastric Age: 55-65 yearsAge: 55-65 years Relieved by food but pain mayRelieved 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 cancerousSmall % become cancerous Severe ulcers may erode throughSevere ulcers may erode through stomach wallstomach wall
  49. 49. Differentiating between H.Differentiating between H. pylori and NSAID-inducedpylori and NSAID-induced ulcerulcer 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
  50. 50. Differential diagnoses forDifferential diagnoses for epigastric painepigastric pain  SurgicalSurgical  Biliary colic, acute cholecystitisBiliary colic, acute cholecystitis  PancreatitisPancreatitis  Perforation of viscusPerforation of viscus  Acute appendicitisAcute appendicitis  MalignancyMalignancy  Hiatus herniaHiatus hernia  MedicalMedical  GORDGORD  MIMI  PEPE  PneumoniaPneumonia
  51. 51. Diagnosis of PUDDiagnosis of PUD
  52. 52. Taking a historyTaking a history 55 yr old man presents with a 6-month history of worsening55 yr old man presents with a 6-month history of worsening epigastric pain described as a burning sensation. He noticesepigastric pain described as a burning sensation. He notices the pain is worse when he is hungry. He feels nauseated withthe pain is worse when he is hungry. He feels nauseated with the pain but has not vomited. There is no change in his bowelthe pain but has not vomited. There is no change in his bowel habits and his weight is more of less stable. He smokes 10habits and his weight is more of less stable. He smokes 10 cigarettes a day and drinks socially. He has been to see hiscigarettes a day and drinks socially. He has been to see his GP who has suggested ranitidine but this has not helped. OnGP who has suggested ranitidine but this has not helped. On examination he is tender in his epigastrium but examinationexamination he is tender in his epigastrium but examination is otherwise unremarkable.is otherwise unremarkable.
  53. 53. Peptic Ulcer DiseasePeptic Ulcer Disease Diagnosis:Diagnosis: 1)1) Diagnosis of ulcerDiagnosis of ulcer 2)2) Diagnosis of H. pyloriDiagnosis of H. pylori
  54. 54.  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
  55. 55. • Niche on the lesser curveNiche on the lesser curve with notch on the greaterwith notch on the greater curvaturecurvature
  56. 56. Diagnosis of PUDDiagnosis of PUD In most patients routine laboratory tests are usuallyIn most patients routine laboratory tests are usually unhelpfulunhelpful Diagnosis of PUD depends mainly on endoscopic and radiographic confirmation
  57. 57. EndoscopyEndoscopy • Most sensitive and specific .Most sensitive and specific . • Direct visualization of the mucosa,Direct visualization of the mucosa, • Biopsy to rule out malignancy orBiopsy to rule out malignancy or Hpylori.Hpylori. • Identifies lesions too small to detect by Ba exam, forIdentifies lesions too small to detect by Ba exam, for evaluation of atypical radiographic abnormalities, or toevaluation of atypical radiographic abnormalities, or to determine if an ulcer is a source of blood loss.determine if an ulcer is a source of blood loss.
  58. 58. Doudenal Ulcer on EndoscopyDoudenal Ulcer on Endoscopy Doudenal UlcerNormal doudenal bulb
  59. 59. Gastric Ulcer on EndoscopyGastric Ulcer on Endoscopy Chronic Gastric Ulcers
  60. 60. Diagnosis ofDiagnosis of H. pyloriH. pylori  Non-invasiveNon-invasive • CC1313 or Cor C1414 Urea Breath TestUrea 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
  61. 61. Diagnosis ofDiagnosis of H. pyloriH. pylori Non-invasive 1. C13 or C14 Urea Breath Test The best test for the detection of an active infection
  62. 62. Diagnosis ofDiagnosis of H. pyloriH. pylori Non-invasiveNon-invasive 1)1) Serology forSerology for H pyloriH pylori a.a. Serum Antibodies (IgG) toSerum Antibodies (IgG) to H pyloriH pylori (Not for active(Not for active infection)infection) b.b. Fecal antigen testing (Fecal antigen testing (Test for active HPTest for active HP))
  63. 63. Diagnosis ofDiagnosis of H. pyloriH. pylori InvasiveInvasive • Upper GI endoscopyUpper GI endoscopy – Highly sensitive testHighly sensitive test – Patient needs sedationPatient needs sedation – Has bothHas both diagnosticdiagnostic && therapeutictherapeutic rolerole
  64. 64. Diagnosis ofDiagnosis of H. pyloriH. pylori Invasive (endoscopy)Invasive (endoscopy) – DiagnosticDiagnostic:: – Detect the site and the size of the ulcer, even smallDetect 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 forBiopsies can be taken for rapid urease testrapid urease test,, histopathologyhistopathology && cultureculture
  65. 65. Diagnosis ofDiagnosis of H. pyloriH. pylori Invasive (endoscopy)Invasive (endoscopy) • Rapid urease test ( RUT)Rapid urease test ( RUT) o Considered the endoscopicConsidered the endoscopic diagnostic test of choicediagnostic test of choice o Gastric biopsy specimens are placed in the rapidGastric biopsy specimens are placed in the rapid urease test kit. Ifurease test kit. If H pyloriH pylori are present, bacterialare present, bacterial urease converts urea to ammonia, which changesurease converts urea to ammonia, which changes pH and produces apH and produces a CCOOLLOORR changechange
  66. 66. Diagnosis ofDiagnosis of H. pyloriH. pylori Invasive (endoscopy)Invasive (endoscopy) * Histopathology* Histopathology o Done if the rapid urease test result is negativeDone if the rapid urease test result is negative * Culture* Culture o Used in research studies and is not availableUsed in research studies and is not available routinely for clinical useroutinely for clinical use
  67. 67. ComplicationsComplications • Complications of GastricComplications of Gastric UlcerUlcer • 1. Hour glass contracture:1. Hour glass contracture: It occurs exclusively inIt occurs exclusively in • women, is due towomen, is due to cicatricial contracture ofcicatricial contracture of lesser curvelesser curve • ulcer.ulcer. • –– Here stomach is dividedHere stomach is divided into two compartmentsinto two compartments
  68. 68. • 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 compartmentPartial gastrectomy wherein gastric ulcer with lower compartment of the stomach is removed and Billroth-I anastomosis is doneof the stomach is removed and Billroth-I anastomosis is done
  69. 69. • 2. Tea-pot deformity:2. Tea-pot deformity: (Hand-Bag stomach) is(Hand-Bag stomach) is duedue to cicatrisation andto cicatrisation and shortening of the lessershortening of the lesser curvature.curvature. • –– They present withThey present with features of pyloricfeatures of pyloric stenosis.stenosis. • –– Treatment is partialTreatment is partial gastrectomy with Billroth-gastrectomy with Billroth- Ianastomosis.Ianastomosis.
  70. 70. • 3. Perforation.3. Perforation. • 4. Bleeding by erosion into the left gastric and rarely splenic4. Bleeding by erosion into the left gastric and rarely splenic vessels or to vessels in the wall of ulcer.vessels or to vessels in the wall of ulcer. • 5. Penetration posteriorly into pancreas, anteriorly into5. Penetration posteriorly into pancreas, anteriorly into liver.liver. • 6. Malignant transformation usually into adenocarcinoma of6. Malignant transformation usually into adenocarcinoma of stomach (2-5%).stomach (2-5%).
  71. 71. TreatmentTreatment • I. General measures: Avoid alcohol, NSAIDs, smoking,spicyI. General measures: Avoid alcohol, NSAIDs, smoking,spicy foods. Have more frequent food.foods. Have more frequent food. • II. Specific measures:II. Specific measures: 1)1) MedicalMedical 2)2) SurgicalSurgical
  72. 72. Drugs of Ulcer treatment
  73. 73. Index…Index…
  74. 74. ClassificationClassification 1.1. Acid Neutralizing agents: (ANTACIDS)Acid Neutralizing agents: (ANTACIDS) • Systemic: Sodium Bicarbonate and Sod. CitrateSystemic: Sodium Bicarbonate and Sod. Citrate • Nonsystemic: Magnesium hydroxide, Mag. Treisilicate, AluminiumNonsystemic: Magnesium hydroxide, Mag. Treisilicate, Aluminium hydroxide gel, Magaldrate and calcium carbonatehydroxide gel, Magaldrate and calcium carbonate 1.1. 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, LansoprazoleOmeprazole, Lansoprazole Pantoprazole, Rabeprazole and EsomeprazolePantoprazole, Rabeprazole and Esomeprazole • Anticholinergics:Anticholinergics: Pirenzepine, Propantheline andPirenzepine, Propantheline and OxyphenoniumOxyphenonium • Prostaglandin analogue:Prostaglandin analogue: MisoprostolMisoprostol
  75. 75. 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 tetracyclinemetronidazole, tinidazole and tetracycline
  76. 76. AntacidsAntacids • Weak bases that neutralize acidWeak bases that neutralize acid • Also inhibit formation of pepsinAlso 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 mEqmEq ofof 1N HCl1N HCl that are broughtthat 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)
  77. 77. Antacids - The Oldest RemedyAntacids - The Oldest Remedy • 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
  78. 78. 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 2Duration 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 andmuscle & delay gastric emptying) – also hypophosphatemia and osteomalciaosteomalcia – Mg2+ antacids – OsmoticMg2+ antacids – Osmotic diarrhoeadiarrhoea • In renal failure Al3+ antacid – Aluminium toxicityIn renal failure Al3+ antacid – Aluminium toxicity & Encephalopathy& Encephalopathy (Magaldrate – hydrated hydroxy magnesium aluminate)(Magaldrate – hydrated hydroxy magnesium aluminate)
  79. 79. 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
  80. 80. Antacids – contd.Antacids – contd. • SimethiconeSimethicone: Decrease surface tension thereby reduce bubble: Decrease surface tension thereby reduce bubble formation - added to prevent refluxformation - 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 anaestheticSurface anaesthetic
  81. 81. Therapeutic QuestionsTherapeutic Questions • Is it rational to combine Aluminium hydroxide and magnesiumIs 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 byHow to avoid formation of insoluble complexes of drugs by antacids, that are not absorbed ?antacids, that are not absorbed ?
  82. 82. Answers (!)Answers (!) • Interactions can be avoided by taking antacids 2 hrs before orInteractions 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 sustainedCombination 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 )
  83. 83. The RealityThe Reality • Not part of Physician prescribed regimen – frequency of dosingNot part of Physician prescribed regimen – frequency of dosing and rebound acidityand rebound acidity • Over the counter (OTC) drug for symptomatic relief ofOver 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
  84. 84. Sucralfate – ulcer protectiveSucralfate – ulcer protective • Salt ofSalt of sucrosesucrose complexed to sulfated aluminium hydroxidecomplexed to sulfated aluminium hydroxide (basic aluminium salt)(basic aluminium salt) • MOA:MOA: – In acidic pHIn 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 – protectiveDelays gastric emptying and causes gastric PG synthesis – protective actionaction
  85. 85. 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 forantagonist 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, hypophosphatemiaADRs: Constipation, hypophosphatemia
  86. 86. Chemical reactions of antacids with HCl in theChemical reactions of antacids with HCl in the stomachstomach
  87. 87. AntacidsAntacids Capsules & Tablets:Capsules & Tablets: • PowdersPowders • Chewable tabletsChewable tablets • SuspensionsSuspensions • Effervescent granules and tabletsEffervescent granules and tablets
  88. 88. ProglumideACh PGE2 Histamine Gastrin Adenyl cyclase _ + ATP cAMP Protein Kinase (Activated) Ca++ + Ca++ Proton pump KK+ H+ Gastric acid Parietal cell Lumen of stomach Antacid Omeprazole Ranitidine H2M3 Misoprostol _ _ _ _ + PGE receptor + + Gastrin receptor+ + +
  89. 89. HH22 AntagonistsAntagonists • Cimetidine, Ranitidine, Famotidine, Roxatidine, NizatidineCimetidine, Ranitidine, Famotidine, Roxatidine, Nizatidine andand • MOA:MOA: – Reversible competitive inhibitors of HReversible competitive inhibitors of H22 receptorreceptor – Highly selective, no action on HHighly selective, no action on H11 or Hor H33 receptorsreceptors – All phases of gastric acid secretionAll phases of gastric acid secretion – Very effective in inhibiting nocturnal acid secretion (as it dependsVery 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 onModest 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
  90. 90. HH22 antagonistsantagonists • 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 urineof the drugs are excreted unchanged in bile and urine • Preparations: available as tablets, injectionsPreparations: available as tablets, injections
  91. 91. HH22 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: – AntiandrogenicAntiandrogenic effectseffects – IncreasesIncreases prolactinprolactin secretion and inhibits degradation ofsecretion and inhibits degradation of estradiolestradiol byby 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
  92. 92. HH22 antagonists - Usesantagonists - Uses Promote 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, RoxMaintenance: 150/20/150 mg BD of R, F, Rox
  93. 93. HH22 blockers Tablets in Peptic ulcerblockers Tablets in Peptic ulcer 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
  94. 94. Proton Pump InhibitorsProton Pump Inhibitors • Most effective drugs in antiulcer therapyMost effective drugs in antiulcer therapy • ProdrugsProdrugs requiring activation in acid environmentrequiring activation in acid environment • Block enzymes responsible for secreting HCl - bindsBlock enzymes responsible for secreting HCl - binds irreversiblyirreversibly toto H+K+ATPaseH+K+ATPase • Prototype:Prototype: Omeprazole (Prilosec)Omeprazole (Prilosec) • Examples:Examples: – LansoprazoleLansoprazole – PantoprazolePantoprazole – RabeprazoleRabeprazole – EsomeprazoleEsomeprazole Omeprazole
  95. 95. Mechanism of actionMechanism of action OmeprazoleOmeprazole 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
  96. 96. 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
  97. 97. QuestionQuestion • Half life of proton pump inhibitors is 1.5 hours only and theseHalf 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)
  98. 98. Pharmacokinetics - PPIPharmacokinetics - PPI  Given on an empty stomach because food affectsGiven on an empty stomach because food affects absorptionabsorption  They should be given 30 minutes to 1 hour before foodThey should be given 30 minutes to 1 hour before food intake because an acidic pH in the parietal cell acidintake because an acidic pH in the parietal cell acid canaliculi is required for drug activation, and foodcanaliculi is required for drug activation, and food stimulates acid productionstimulates acid production  Concomitant use of other antisecretory drugs - H2 receptorConcomitant use of other antisecretory drugs - H2 receptor antagonists – reduces actionantagonists – reduces action  Highly protein bound and rapidly Metabolized by the liverHighly protein bound and rapidly Metabolized by the liver by CYP2C19 and CYP3A4 – dose reduction necessary inby CYP2C19 and CYP3A4 – dose reduction necessary in severe hepatic failuresevere hepatic failure  Excreted in Kidneys minimally (no dose reduction neededExcreted in Kidneys minimally (no dose reduction needed in renal failure and elderly)in renal failure and elderly)
  99. 99. 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 rashesSubacute 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 reboundHypergastrinemia which may predispose to rebound hypersecretion of gastric acid upon discontinuation of therapy andhypersecretion of gastric acid upon discontinuation of therapy and may promote the growth of gastrointestinal tumors (carcinoidmay promote the growth of gastrointestinal tumors (carcinoid tumors )tumors )
  100. 100. • 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 ulcers 3.3. Bleeding peptic UlcerBleeding peptic Ulcer 4.4. Zollinger ellison SyndromeZollinger ellison Syndrome 5.5. Prevention of recurrence of nonsteroidal antiinflammatory drugPrevention 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 withReducing the risk of duodenal ulcer recurrence associated with H. pylori infectionsH. pylori infections 7.7. Aspiration PneumoniaAspiration Pneumonia
  101. 101. 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.
  102. 102. Muscarinic antagonistsMuscarinic antagonists Atropine:Atropine: – Block the MBlock the M11 class receptorsclass 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 muscarinicReduce 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 ofUnpopular as a first choice because of high incidence of anticholinergic side effects (dry mouth and blurredanticholinergic side effects (dry mouth and blurred vision)vision)
  103. 103. 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
  104. 104. Prostaglandin analogues -Prostaglandin analogues - MisoprostolMisoprostol Actions:Actions: Inhibit histamine-stimulated gastric acid secretionInhibit histamine-stimulated gastric acid secretion Stimulation of mucin and bicarbonate secretionStimulation of mucin and bicarbonate secretion Increase 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 injuryPrevent 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)
  105. 105. 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 shouldExacerbations 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)
  106. 106. QuestionQuestion A patient comes to your clinic at midnight complaining of heartA patient comes to your clinic at midnight complaining of heart burn. You want to relieve his pain immediately. What drugburn. You want to relieve his pain immediately. What drug will you choose?will you choose?
  107. 107. Answer isAnswer is AntacidsAntacids • Explanation :Explanation : Antacids neutralize the already secreted acid in theAntacids neutralize the already secreted acid in the stomach. All other drugs act by stopping acid secretion and sostomach. 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
  108. 108. Eradication of H.pylori Omeprazole Amoxicillin Clarithromycin Metronidazole
  109. 109. Triple Therapy The 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
  110. 110. 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
  111. 111. Bismuth subsalicylateBismuth subsalicylate Pharmacological actions:Pharmacological actions: • Undergoes rapid dissolution in the stomach into bismuth andUndergoes rapid dissolution in the stomach into bismuth and salicylatessalicylates • Salicylates are absorbedSalicylates are absorbed • Bismuth coats ulcers and erosions protecting them from acidBismuth coats ulcers and erosions protecting them from acid and pepsin and increases prostaglandin and bicarbonateand pepsin and increases prostaglandin and bicarbonate productionproduction • Uses:Uses: • Treatment of dyspepsia and acute diarrhoeaTreatment of dyspepsia and acute diarrhoea
  112. 112. Question A pregnant lady (first trimester) comes to you with peptic ulcer disease. Which drug will you prescribe for her ?
  113. 113. 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
  114. 114. Emergency scenarioEmergency scenario • A 50 year old man is brought into A+E via ambulance. He isA 50 year old man is brought into A+E via ambulance. He is vomiting bright red blood and complaining of abdominal pain.vomiting bright red blood and complaining of abdominal pain. You get a quick history from his wife who explains he suffersYou get a quick history from his wife who explains he suffers with heartburn and is on lansoprazole. He was out with hiswith heartburn and is on lansoprazole. He was out with his work mates last night and drank quite heavily.work mates last night and drank quite heavily.
  115. 115. Initial Management IInitial Management I • ABCDE approachABCDE approach • Call for helpCall for help
  116. 116. 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 cannulaeGain access – 2 large bore cannulae – Bloods- FBC, U&Es, LFTs, glucose, clotting, cross match 6 unitsBloods- FBC, U&Es, LFTs, glucose, clotting, cross match 6 units – Catheterise to monitor urine outputCatheterise to monitor urine output
  117. 117. 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 30%Red cell transfusion should be considered after loss of 30% of the circulating volumeof the circulating volume • Correct any clotting abnormalitiesCorrect any clotting abnormalities • Urgent endoscopy after resuscitationUrgent endoscopy after resuscitation
  118. 118. Acute upper GI bleedAcute upper GI bleed • Common, 10% mortalityCommon, 10% mortality • Common causes: PUD, varicesCommon causes: PUD, varices • Endoscopy: primary diagnostic investigation & allows forEndoscopy: primary diagnostic investigation & allows for treatmenttreatment • Assess using the Blatchford score at first assessment and fullAssess using the Blatchford score at first assessment and full Rockall score after endscopyRockall score after endscopy
  119. 119. 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 falseUrea 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 controlledevaluate symptoms after one month. Patients who are controlled should cont. 2-4 more weeks.should cont. 2-4 more weeks.
  120. 120. SummarySummary  A peptic ulcer is a break in superficial epithelial cells penetratingA peptic ulcer is a break in superficial epithelial cells penetrating down to muscularis mucosadown to muscularis mucosa  Duodenal > gastric ulcersDuodenal > 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 ifH pylori diagnosed by c urea breath test, stool antigen or if validated serology, treated with PAC500 or PMC250 regimevalidated serology, treated with PAC500 or PMC250 regime  Complications of PUD can lead to acute emergency of upper GIComplications of PUD can lead to acute emergency of upper GI bleedbleed
  121. 121. H. pyloriH. pylori Thank UThank U 

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