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A.P.D. presentation by Prof.JaAkram

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  • So basically this was a presentation to promote ulcocid, a brand of sucralfate made by Don Valley pharm. This is the worth of these professors in Pakistan, they sell themselves for few rupees. Even their undergarments are given by medical reps. Shame on you Javed Akram ...
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A.P.D. presentation by Prof.JaAkram A.P.D. presentation by Prof.JaAkram Presentation Transcript

  •  
  • New Perspectives in The Management of Peptic Ulcer Disease. Professor Javed Akram. Mb, MEE(Can), MRCP(UK), FRCP(Glasg), FRCP(Edin), FRCP(London), FACP(USA), FASIM(USA), FACC(USA).
  • Peptic Ulcer Disease
    • A peptic ulcer is a break (an ulceration) in the protective mucous lining (mucosa) of the lower esophagus, stomach or duodenum
  • Common Misconceptions
    • A peptic ulcer is NOT:
      • A stress ulcer
      • Chronic gastritis (a symptom as well as a disease state that may lead to peptic ulcers)
      • Dyspepsia (the symptoms that may or may not be diagnosed as an ulcer)
    • Peptic Ulcers cannot be diagnosed solely on the basis of clinical presentation (Werdmuller et al. 1996)
  • Dyspepsia.
  • Dyspepsia - Definition
    • A group of symptoms which alert clinicians to consider disease of the upper gastrointestinal tract
    (British Society of Gastroenterology, 1996)
  • Symptoms of Functional Dyspepsia Ulcer-like Dominant Dysmotility-like Dominant Nocturnal pain Localized epigastric burning Better with food Heartburn Retrosternal burning Nausea Bloating Early satiety Worse with food
  • Quick Stats:Peptic Ulcer
    • 5-10% lifetime incidence
    • 1-2% of people have ulcer at any given time
    • $5.65 billion industry
  • Peptic Ulcer Hospitalization Rates Kurata JH. Semin Gastrointest Dis 1993:4 Rate per 100,000 Gastric Ulcer Duodenal Ulcer 70 75 80 85 90 0 20 40 60 80 100 Uncomplicated Hemorrhage Perforation 70 75 80 85 90 0 20 40 Year Year 30 10 Uncomplicated Hemorrhage Perforation
  • Types
    • Gastric
      • Slightly more common in men and way more common in elderly
      • Most commonly located in the stomach’s lesser curvature, antrum
      • 1-3% associated with gastric carcinomas
      • Basic defect is disruption of gastric mucosal barrier (gastritis, duodenal reflux, H. pylori, NSAIDS)
  • Types
    • Duodenal
      • Almost always located in the duodenal bulb
      • More likely culprit in chronic disease
      • No association with cancer
  •  
  •  
  • Risk Factors
    • Smoking
      • 33-100% more likely to develop duodenal ulcers
      • Retards healing of identified ulcers
      • J Akram& Colleagues .. E.J.of Gastrenterology.Nov2003)
    • Age and Sex
    • Alcohol
    • Diet
      • Milk
    • Stress
    • Ramadan fasting
  • Risk Factors
    • NSAIDS
      • Responsible for majority of ulcers not caused by H.pylori
      • Greater risk for complications once ulcer identified
      • Risk of GU increases sixfold when taking >three aspirin/day. Buffered coat has no advantage
  • Prevalence of Endoscopic NSAID-Induced Ulceration
    • Mean Range
    • Gastric Ulcer 15 % 10 to 30%
    • Duodenal Ulcer 5 % 4 to 10 %
    • Clinically Significant Ulcers 2% 1 to 4%
  • Risk Factors for Serious GI Adverse Events with NSAIDs: Relative Risks Rodriguez. Lancet. 1994; Guttham. Epidemiology. 1997; Shorr. Arch Intern Med. 1993; Piper. Ann Intern Med. 1991. 0 5 10 15 4.4 (2.0-9.7) 12.7 (6.3-25.7) 2.9 (2.2-3.8) 5.8 (4.0-8.6) 5.6 (4.6-6.9) 3.1 (2.5-3.7) 1.6 (1.4-2.0) 13.5 (10.3-17.7) Corticosteroid use Anticoagulant use Low dose NSAID High dose NSAID Age 70-80 Age 60-69 Age 50-59 Prior bleed Relative Risk
  • NSAID ↑ Leukocyte-Endothelial Interactions Capillary Obstruction Ischemic Cell Injury Proteases + Oxygen Radicals Endo/Epithelial Cell Injury Mucosal Ulceration Loss of PGE 2 and PGI 2 mediated inhibition of acid secretion and cytoprotective effect Loss of PGI 2 induced inhibition of LTB 4 mediated endothelial adhesion and activation of neutrophils
  • Peptic Ulcers and Stress
    • Experimental stress results in decreased upper gastrointestinal blood flow in animals
      • (Kauffman, 1997; Livingston 1993)
    • Effect of stress seems to be reversible
      • (Levenstein et al., 1996)
  • Peptic Ulcer and Personality
    • Studies have found a strong association between dependency and peptic ulcers
    • Patients with peptic ulcer have significantly more personality disturbances than control subjects (Feldman et al.)
    • Ulcer patients also more inclined to pessimism and excessive dependence (Akram et al.)
  •  
  • Helicobacter pylori
    • Gram-negative spiral organism
    • Most common and important risk factor for duodenal ulcer
    • Variable risk factor for gastric ulcers
    • 10% healthy people under 30, 60% healthy people over 60.
    • Will cause disease in 15-20% of infected
    • Eradication is the key
  • Diagnosis of Peptic Ulcer
  • Diagnosis
    • Vague discomfort and feeling of gnawing hunger
    • Duodenal usually has predictable food relationship (1-3 hrs after meal)
    • Gastric ulcer relationship with food more variable
    • Gastric ulcer-weight loss
    • Duodenal ulcer-weight gain
    • Watch for peptic ulceration/bleeding: melena, radiation of pain to back/shoulder
  • Physical Exam
    • Epigastric tenderness
    • Rectal exam!!
  • Studies
    • Radiography
      • Barium swallow with double contrast
      • Duodenal-detects 40-80%
      • Gastric-detects 65-80%
    • Endoscopy
      • Gold standard
      • Detects up to 95% gastroduodenal ulcers
      • Generally considered the study of choice esp. for large ulcers or those not clearly benign
  • Diagnosis of H. pylori
    • Invasive (if patient requires endoscopy)
      • Histologic testing (50-90% sensitive, 100% specific)
      • Rapid urease (CLO) test (95% sensitive and 95% specific)*
    • Noninvasive
      • IgG antibody*
      • Urea breath test (96% sensitive, 98% specific)
  • Complications
    • Perforation
    • Reoccurrence
    • Obstruction
    • Bleeding
    • Cancer
  • Upper GI Bleeding
  • A common medical condition
    • 250,000 – 500,000 admissions/year in US
    • UGI bleeding incidence 100/100,000 adults
      • Incidence increases 20-30 fold from third to ninth decade of life
    • GI bleeding stops spontaneously in 80 %
  • Bleeding Stats:Mayo J.Akram etal 2001PJGE
  • Therapy
    • Goal is to heal the ulcer and prevent recurrence
    • Both can be accomplished by eradicating H. pylori if present
    • Treat the acute pain if necessary
  • Nonpharmacologic
    • There is no evidence that dietary modifications changes the course of the disease
    • Quit smoking
    • Milk intake
    • Faster healing, lower recurrence, lower complications
    • Discontinue NSAIDS
    • COX2 Inhibitors?
  • Treatment of ulcers
    • Eradicate H. pylori
    • Single antibiotic therapy does not work
    • Compliance is key
      • More than 60% of the doses must be taken to ensure eradication
    • If eradicated, maintenance therapy not needed. If recurs, check for H. pylori again
    • If H. pylori not found, check again and treat with H2-receptor antagonists, PPI’s and sucralfate
    • Document healing of gastric ulcers with endoscopy
  • ULCOCID (Sucralfate)
  • Chemical Structure of Sucralfate
    • Sucrose Octasulphate Poly aluminum Hydroxide
    • Sucralfate
    • C 12 H 6 O 11 [SO 3 Al 2 (OH) 5 ] n H 2 O
  • ULCOCID (Sucralfate)
    • 1. Non systemic
    • 2. Cytoprotective
    • 3. Acid related disorders
  • PHAMACOKINETICS
    • ABS0RPTION
    • Minimal absorption by GIT 3-5%
    • EXCRETION
    • Approximately 90% is excreted in the stool, very
    • small amount is excreted in the urine.
  • INDICATIONS OF ULCOCID
    • Duodenal ulcers
    • Gastric ulcers
    • treatment of reflux and peptic oesophagitis
    • H.pylori
    • treatment of NSAID & aspirin induced GI symptoms and mucosal damage.
    • Prevention of stress ulcers and GI bleeding in critically ill patients.
    • Treatment of oral and oesophageal ulcers due to radiation chemotherapy & sclerotherapy.
    • Sucralfate enemas in ulcerative colitis & colonic carcinomas
  • AVAILABILITY OF DRUG
    • ULCOCID tablets
    • ( containing 500 mg Sucralfate per tablet ).
    • ULCOCID tablets
    • ( containing 1 g Sucralfate per tablet ).
    • ULCOCID Susp. 60 ml
    • ( containing 1 g Sucralfate per 5ml).
  • DOSAGE RECOMMENDATION OF ULCOCID
    • For Ulcer Patients
    • Morning
    • 2g Ulcocid
    • Evening
    • For Non Ulcer Patients
    • Morning
    • 1 g Ulcocid
    • Evening
  • ULCOCID
    • ULCOCID should always be taken 1 hour before meals at bed time (Monotherapy)
    • Do not take antacids 1/2 hour before or after taking ULCOCID (Polytherapy) .
  • ANTACIDS Vs ULCOCD
    • ANTACIDS
    • Just symptomatic therapy.
    • Intense antacid regimen required for healing.
    • Not safe for hypertensive or cardiac patients.
    • Non-Palatable.
    • Not suitable for working class because of frequent dose taken.
    • ULCOCID
    • Ulcer healing occurs.
    • None
    • Palatable
    • Dosage is convenient.
  • Ulcocid Vs H2- Receptor Antagonists
    • Ulcocid
    • Less side effects
    • Can be administered to elderly.
    • Smokers can use it.
    • Does not effect hepatic metabolism of drugs.
    • Does not effect pulmonary functions in patients with pre-existing broncho- pulmonary diseases.
    • H2-Receptor Antagonists
    • More side effects
    • Causes hallucination and delirium in elderly
    • Only for non- smokers.
    • Does effect the metabolism of drugs metabolized by Cytochrome P-450 path-way.
    • H2 – blockers may worsen the condition.
  • Human Studies.
    • Comparative evaluation of Sucralfate & Cimetidine efficacy in treatment of chronic erosive gastritis.
    • The results of patients with chronic erosive gastritis treated with Sucralfate & Cimetidine were compared. The result of examinations indicate that chronic erosive gastritis is difficult to be heal; Sucralfate proved to be more efficient than Cimetidine.
    • Ref: Au:Kula-Z:Walasek-L So:Pizegl-Lek 1998; 51(2): 73-6
  • Meta-analysis:Human Studies.
    • Comparative evaluation of Sucralfate & Cimetidine efficiency in treatment of chronic erosive gastritis proved that Sucralfate is more efficient than Cimetidine.
    • Ref: Au: Kula-Z:Walasek-L So:Pizegl-Lek 1999; 51(2): 73-6
  • ULCOCID Vs ACID PUMP INHIBITORS
    • Acid Pump Inhibitors
    • Jaundice has been reported.
    • Hypoglycaemia, Wt. Gain.
    • Increased intragastric concentrations of viable bacteria during the T/M.
    • Ulcocid
    • No jaundice reported
    • None
    • None
  • Anti Helicobacter effects Omeprazole Vs Ulcocid (With Clarithromycin and Metronidazole)
  • Ulcocid Counters the Effect of H.Pylori on Gastric Mucosa
    • H.PYLORI
    •  Mucus viscosity
    •  Glycoproteins & lipids
    •  Na+/H+ exchange of mucus
    •  Mucosal bicarbonate secretion
    •  Cell desquamation
    •  Mucosal microvessel permeability
    •  Mucosal blood flow?
    •  Surface hydrophobicity
    •  Cell membrane permeability
    •  H+ Back diffusion.
    • ULCOCID
    •  Mucus viscosity
    •  Glycoproteins & lipids
    •  Na+/H+ exchange of mucus
    •  Mucosal bicarbonate secretion
    •  Mucosal PGE2, Mucosal renewal
    •  Mucosal blood flow
    •  Surface hydrophobicity
    •  Cell membrane permeability
    •  H+ Back diffusion.
  • HUMAN AND ANIMAL STUDIES
    • Invitro and clinical data suggest that triple therapy with SUCRALFATE is effective in eradicating HELICOBACTER PYLORI and reducing duodenal ulcer relapse.
    • Ref: Louw- Ja So:Scand-J-Gastroenterol-Suppl. 1998; 191:28-31
  • Human Studies
    • Glycosulfatase activity of H. Pylori towards human gastric mucin; effect of Sucrafate.
    • Results demonstrate that H. Pylori, through its Glycosulfatase activity affects the sulphated mucin & glycero-gluco-lipid content of the protective mucous layer & that anti-ulcer drug Sucralfate is able to counteract the detrimental action of this enzyme.
    • Ref: Slomiany-BL; Piotrowski-J; Grabska-M; SLOMIANY-a So: Am-j-Gastroenterol. 1999 Sep; 87(9); 1132-7
  • ULCOCID INHIBITS THE EFFECT OF H.Pylori on gastric mucins
  • ULCOCID
    • Direct binding to ulcer crater
    • Stimulates prostaglandin production
    • Enhances the surface active phospholipid mucosal barrier.
    • Stimulates growth factors
    • . Epidermal
    • . Transforming
    • . Fibroblast
    • Anti-helicobacter effects.
  • Recurrent Aphthous Stomatitis (RAS)
    • Minor apthae
  • Recurrent Aphthous Stomatitis (RAS)
    • Major apthae
  • Sucralfate in apthous ulcers. F.Khan,A.Awan,J.Akram SMJ,Jun,2003
    • Statistically significantly better pain relief
    • Earlier ulcer healing rates
    • Better QOL
  • Sucralfate Enema
    • Ulcerative Colitis
    • Ca.Colon
  • HUMAN STUDIES
    • Management of bleeding in a patient with colorectal cancer:
    • SUCRALFATE an oral cytoprotective, used topically in a patient with colo-rectal cancer resulting in control of bleeding, less localized pain and more freedom & independence for the patient.
    • Ref: Au: Famcombe-M So: Support-care-cancer, 1993 May;1(3):159-60.
  • WHY ULCOCID ?
    • Fast pain relief.
    • Excellent healing rate.
    • Equal good for smokers and non - smokers.
    • Good for elderly.
    • Equally good for ulcer and non - ulcer patients.
    • Economical
  • Thank You.