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  • Table 3. Factors Predictive of a Sustained Beneficial Response to Interferon Alfa in Patients with Chronic Hepatitis.
  • Table 3. Characteristics of Hepatitis A Virus, Hepatitis B Virus, and Hepatitis C Virus.
  • Figure 2. The Replication Cycle of HBV. HBV virions bind to surface receptors and are internalized. Viral core particles migrate to the hepatocyte nucleus, where their genomes are repaired to form a covalently closed circular DNA (cccDNA) that is the template for viral messenger RNA (mRNA) transcription. The viral mRNA that results is translated in the cytoplasm to produce the viral surface, core, polymerase, and X proteins. There, progeny viral capsids assemble, incorporating genomic viral RNA (RNA packaging). This RNA is reverse-transcribed into viral DNA. The resulting cores can either bud into the endoplasmic reticulum to be enveloped and exported from the cell or recycle their genomes into the nucleus for conversion to cccDNA. The small, peach-colored sphere inside the core particle is the viral DNA polymerase.
  • Figure 2. The Natural History of HCV Infection and Its Variability from Person to Person. The course of infection varies widely among persons. Factors that decrease the risk of progression include female sex and a younger age at infection; factors that increase the risk include alcohol intake, an older age at infection, male sex, and coinfection with other viruses. Persons with a favorable risk profile often do not have progressive liver disease until 30 or more years after infection. In contrast, 20 percent of persons with chronic hepatitis C will eventually have cirrhosis, and this can occur 20 years or less after infection, especially in those with alcohol abuse or coinfection with human immunodeficiency virus type 1 or hepatitis B virus. Once cirrhosis is established, the risk of hepatocellular carcinoma is 1 to 4 percent per year.
  • Table 2. Side Effects of Treatment with Interferon Alfa and Ribavirin.
  • Figure 2. Pathogen-Host Interactions in the Pathogenesis of Helicobacter pylori Infection. The host response to H. pylori participates in the induction of damage to the gastric epithelium and therefore has an integral role in H. pylori pathogenesis. During the early phase of the infection, binding of H. pylori to gastric epithelial cells, in particular through BabA and by strains harboring the cag pathogenicity island, results in the production of interleukin-8 and other chemokines, such as epithelial-cell-derived neutrophil-activating peptide 78 (ENA-78) and growth-related oncogene {alpha} (GRO-{alpha}), by epithelial cells. Nuclear factor-{kappa}B (NF-{kappa}B) and the early-response transcription-factor activator protein 1 (AP-1) are the intracellular messengers involved in this process. The chemokines secreted by epithelial cells bind to the proteoglycan scaffolding, generating a gradient along which polymorphonuclear cells (PMN) are recruited. The chronic phase of H. pylori gastritis associates an adaptive lymphocyte response with the initial innate response. Lymphocyte recruitment is facilitated by chemokine-mediated expression of vascular addressins such as vascular-cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) that are required for lymphocyte extravasation. Macrophages that participate in interleukin-8 production produce proinflammatory cytokines involved in the activation of the recruited cells, in particular T helper cells (Th0, Th1, Th2), that respond with a biased Th1 response to H. pylori. In turn, Th1-type cytokines such as interferon-{gamma} (INF-{gamma}) induce the expression of class II major histocompatibility complexes (MHC) and accessory molecules B7-1 and B7-2 by epithelial cells, making them competent for antigen presentation. The cytotoxin VacA- and Fas-mediated apoptosis induced by tumor necrosis factor {alpha} (TNF-{alpha}) leads to disruption of the epithelial barrier, facilitating translocation of bacterial antigens and leading to further activation of macrophages. Cytokines produced by macrophages can also alter the secretion of mucus, contributing to H. pylori-mediated disruption of the mucous layer. Cytokines produced in the gastric mucosa induce changes in gastric-acid secretion and homeostasis (dashed lines). TNF-{alpha}, interleukin-1{beta}, and interferon-{gamma} increase gastrin release, stimulating parietal and enterochromaffin cells and thus acid secretion. TNF-{alpha} also induces a decrease in the number of antral D cells, leading to decreased somatostatin production and indirectly enhancing acid production. LPS denotes lipopolysaccharide.
  • Transcript

    • 1. GI Pharmacology INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com www.indiandentalacademy.com
    • 2. Topics        Peptic ulcer disease/dyspepsia GORD Inflammatory bowel disease Irritable bowel syndrome Diarrhoea Constipation Pancreatitis www.indiandentalacademy.com
    • 3. Dyspepsia / Peptic ulcer disease Dyspepsia: upper abdo pain/discomfort (fullness, bloating, distension, nausea) Peptic ulcers defects in mucosa extending through muscularis mucosae Prevalence PUD 5-10% lifetime dyspepsia 25-40% Aetiology (most common)  H.pylori  NSAIDs www.indiandentalacademy.com
    • 4. www.indiandentalacademy.com
    • 5. Mucosa protective factors www.indiandentalacademy.com
    • 6. Parietal cell and acid regulation www.indiandentalacademy.com
    • 7. NSAIDs       Antiinflammatory Analgesic Antipyretic Chemically heterogeneous Reversible competitive inhibitors of COX activity (Aspirin irreversible) Reduce prostaglandin synthesis (COX-1)        ↓ Mucus ↓ bicarbonate ↓ blood flow ↓ proliferation of cells ↑ gastric acid secretion Reduce production of superoxide radicals, induce apoptosis, inhibit expression of adhesion molecules, decrease NO synthase and proinflammatory cytokines, modify lymphocyte activity and alter cellular membrane functions Biliary excretion and reflux of metabolites into stomach www.indiandentalacademy.com
    • 8. Helicobacter pylori    Peptic ulcers Gastric carcinoma/lymphoma Mucosal atrophy Tests      Urea breath test (sens. and spec. ~95%) Endoscopic (urease, histology) Stool antigen (sens. and spec. ~ 95%) (serology) Omit PPI for 2 weeks prior to tests www.indiandentalacademy.com
    • 9. H. pylori www.indiandentalacademy.com
    • 10. Management of dyspepsia    Therapeutic trial of acid suppressing medication H. pylori screening If alarm features         GI bleeding Unintentional weight loss Progressive dysphagia Odynophagia Persistant vomiting Iron deficiency anaemia Mass/ suspicious barium meal Do Endoscopy www.indiandentalacademy.com Gastric ulcer
    • 11. Treatment Lifestyle advice   Diet (alcohol, caffeine…) Smoking Medication       Stop NSAIDs if possible H-2 receptor antagonists Proton pump inhibitors H. pylori eradication Antacids Misoprostol (NSAIDs) www.indiandentalacademy.com
    • 12. H2 receptor antagonists  Cimetidine, Ranitidine, Famotidine, Nizatidine  Competitive and selective inhibition of histamine H-2 receptor Suppress 24 hr gastric secretion by 70% Less effective than PPI      Caution: Interaction: renal failure, pregnancy, breast feeding Cimetidine binds to CYP 450 (retards oxidative drug metabolism) note interactions with warfarin, phenytoin, theophylline.. Side effects     Well tolerated, less than 3% adverse effects Diarrhoea, headache, drowsy, fatigue, constipation, CNS, LFT Rarely pancreatitis, bradycardia, AV block, confusion (elderly, especially cimetidine) Rarely blood dyscrasias www.indiandentalacademy.com
    • 13. Proton pump inhibitors  Omeprazole, Lansoprazole, Pantoprazole, Esomeprazole, Rabeprazole  Prodrugs activated in acidic secretory canaliculi Inhibit gastric H+K+ ATPase irreversibly Decrease acid secretion by up to 95% for up to 48 hours     Use: Ulcers, GORD, Zollinger-Ellison Syndrome, reflux oesophagitis Side effects      Generally well tolerated mc Gastrointestinal, headache, headache dizziness Omeprazole – impotence, gynaecomastia May increase risk of GI infections (reduced acidity) Note: pH > 6 necessary for platelet aggregation Give high dose PPI in active GI bleed (eg Omeprazole 8mg/hr for 72 hrs) www.indiandentalacademy.com
    • 14. H. pylori eradication    Eradication increases ulcer healing Reduces recurrence MALT, Ca (can lead to resolution) Triple therapy For 7 (14) days twice daily eg    full dose PPI + Amoxicillin + Clarithromycin/Metronidazole Effective in 80-85% www.indiandentalacademy.com
    • 15. Other Antacids     Mg and Al hydroxides May chelate other drugs (avoid concomitant administration of other drugs) Side effects: diarrhoea (Mg), constipation (Al) Milk alkali syndrome (alkalosis, renal insufficiency, hypercalcemia) Sucralfate     Forms sticky polymer in acidic environment Inhibits hydrolysis of mucous proteins by pepsin 1 g bd to 1g qds SE: constipation, aluminium absorption (avoid in severe renal impairment due to risk of encephalopathy) www.indiandentalacademy.com
    • 16. Misoprostol    PGE1 analogue Stimulates Gi pathway (↓cAMP and ↓gastric acid) ↑ blood flow and ↑ mucus and bicarbonate secretion Use: prevention of NSAID induced injury Side effects: diarrhoea, pain, cramps (30%) Can cause exacerbation of IBD Contraindication: pregnancy, caution in women of childbearing age can induce labour! www.indiandentalacademy.com
    • 17. Nonvariceal Upper GI Bleed    Resuscitate (iv access, fluids, catheter, transfusion) Bloods (cross match, FBC, U&E, clotting) Drugs      Acid suppressing drugs (stabilize clot) Somatostatin – reduces acid secretion and splanchnic blood flow Antifibrinolytic drugs – tranexamic acid reduces need for surgery and mortality +/- transfuse Endoscopy: cause of bleeding, haemostasis (injection, clips, banding...), can usually wait until next day www.indiandentalacademy.com
    • 18. GORD Definition   Abnormal reflux of gastric contents into oesophagus ± mucosal damage Prevalence   > 50% of population > once a year 50% of patients have erosive oesophagitis Pathophysiology   Antireflux barrier (sphincter…) Acid, pepsin, trypsin, bile acids, hiatus hernia www.indiandentalacademy.com
    • 19. Symptoms     Heartburn Belching Asthma, cough Hoarseness, sore throat, globus Alarm features        GI bleeding Unintentional weight loss Progressive dysphagia Odynophagia Persistent vomiting Iron deficiency anaemia Mass/ suspicious barium meal www.indiandentalacademy.com
    • 20. Precipitants     Food (fatty food, alcohol, caffeine) Smoking Obesity Medication   calcium antagonists, nitrates, theophyllines, NSAIDs, corticosteroids Pregnancy Usually chronic relapsing course www.indiandentalacademy.com
    • 21. Diagnosis    Symptoms Empirical therapy Endoscopy     Failure of response to therapy Alarm features Barrett’s 24-hour pH monitoring   pH < 4 Limited sensitivity www.indiandentalacademy.com
    • 22. Complications    Oesophagitis Strictures, ulcers Barrett's www.indiandentalacademy.com
    • 23. Barrett's    Intestinal columnar metaplasia Malignant potential Needs surveillance www.indiandentalacademy.com
    • 24. Treatment Lifestyle advice      Dietary habits (fat, alcohol, caffeine, timing) Smoking Weight loss Raising head But little evidence for all those Medication     H-2 receptor antagonists PPI Antacids Prokinetics www.indiandentalacademy.com
    • 25. Inflammatory Bowel Disease Ulcerative colitis  Diffuse mucosal inflammation limited to the colon Crohn's disease   Features  UC  CD patchy transmural inflammation May affect any part of GI tract bloody diarrhoea, colicky pain, urgency, tenesmus abdominal pain, diarrhoea, weight loss intestinal obstruction systemic symptoms www.indiandentalacademy.com
    • 26. Drugs in IBD       Aminosalicylates Corticosteroids Thiopurines Methotrexate Ciclosporin Infliximab www.indiandentalacademy.com
    • 27. Aminosalicylates     Sulfasalazine (5-aminosalicylic acid and sulfapyridine as carrier substance) Mesalazine (5-ASA), eg Asacol, Pentasa Balsalazide (prodrug of 5-ASA) Olsalazine (5-ASA dimer cleaves in colon)  Oral, rectal preparation  Use Maintaining remission  Active disease  May reduce risk of colorectal cancer Adverse effects  10-45%  Nausea, headache, epigastric pain, diarrhoea, hypersensitivity, pancreatitis, blood disorders, lung disorders, myo/pericarditis  Caution in renal impairment, pregnancy, breast feeding   www.indiandentalacademy.com
    • 28. Corticosteroids  Antiinflammatory agents for moderate to severe relapses eg 40mg Prednisolone Inhibition of inflammatory pathways (↓IL transcription, suppression of arachidonic acid metabolism, lymphocyte apoptosis)  Side effects       Acne, moon face, oedema Sleep, mode disturbance Dyspepsia, glucose intolerance Cataracts, osteoporosis, myopathy… www.indiandentalacademy.com
    • 29. Thiopurines Azathioprine, mercaptopurine    Inhibit ribonucleotide synthesis Inducing T cell apoptosis by modulating cell signalling Azathioprine metabolised to mercaptopurine and 6-thioguanine nucleotides Use   Active and chronic disease Steroid sparing Side effects    Leucopaenia (myelotoxic) Monitor for signs of infection, sore throat Flu like symptoms after 2 to 3 weeks, liver, pancreas toxicity www.indiandentalacademy.com
    • 30. Methotrexate   Inhibits dihydrofolate reductase Probably inhibition of cytokine and eicosanoid synthesis Use  Relapsing or active CD refractory or intolerant to AZA or Mercaptopurine  Monitor FBC, LFT Side effects  GI  Hepatotoxicity, pneumonitis www.indiandentalacademy.com
    • 31. Ciclosporin Inhibitor of calcineurin, preventing clonal expansion of T cell subsets Use     Active and chronic disease Steroid sparing Bridging therapy Side effects    Tremor, paraesthesiae, malaise, headache, abnormal LFT Gingival hyperplasia, hirsutism Major: renal impairment, infections, neurotoxicity Monitor  Blood pressure, FBC, renal function www.indiandentalacademy.com
    • 32. Infliximab   Anti TNF-α monoclonal antibody Potent anti inflammatory effects Use  Fistulizing CD  Severe active CD refractory/intolerant of steroids or immunosuppression  iv infusion Side effects  Infusion reactions  Sepsis  Reactivation of Tb, increased risk of Tb www.indiandentalacademy.com
    • 33. Principles of Managment of IBD  Assess severity  Mild and distal   Diffuse or not responding –   add oral steroids Severe   topical steroids/aminosalicylates admit, iv steroids, iv fluids, ?TPN etc Ulcerative colitis:  Avoid antimotility drugs and antispasmodics as may precipitate paralytic ileus and megacolon www.indiandentalacademy.com
    • 34. Medical management of UC Active left sided/extensive      Aminosalicylate eg Mesalazine Prednisolone 40mg (for prompt response or if mesalazine unsuccessful) – reduce dose gradually Azathioprine for steroid dependant disease Topical agents (rectal symptoms) Ciclosporin for severe, steroid refractory colitis Active distal UC   Mild/Mod topical mesalazine (or steroid) + oral mesalazine +/- oral steroids www.indiandentalacademy.com
    • 35. Severe UC    Admission for iv therapy Close monitoring  Daily physical examination, regular vital signs, stool chart, CRP, AXR  FBC, ESR, CRP, U&E, albumin, LFT every 24-48 hours  Daily AXR if colonic dilatation (transverse >5.5cm) Therapy  iv fluids and electrolytes if necessary  sc heparin (thromboembolism prophylaxis)  ? Nutritional support  iv steroids  Withdrawal of antidiarrhoeal agents (can precipitate dilatation)  Aminosalicylates  Topical therapy +/- surgical referral (colonic dilatation) Stool frequency (>8) and CRP (>45) on day 3 predict need for surgery Consider colectomy or iv ciclosporin www.indiandentalacademy.com
    • 36. Medical Management of CD  Assessment    Active intestinal disease         Mild – aminosalicylate Mod/severe – oral corticosteroids (reduce gradually over 8 weeks) Severe – iv steroids Elemental/polymeric diets TPN (fistulating) Azathioprine as steroid sparing agent Consider surgery Fistulating and perianal     Site, pattern (inflammation, stricturing, fistulating), prior disease activity Confirm disease activity (CRP, ESR) Metronidazole +/- ciprofloxacin Azathioprine Infliximab Other sites www.indiandentalacademy.com
    • 37. Maintenance of remission of CD      STOP SMOKING Mesalazine of limited benefit Azathioprine effective but toxicity Methotrexate Infliximab Steroid refractory disease  Definition     Active disease on >20 mg prednisolone > 2 weeks Relapse when dose reduction Azathioprine (monitor FBC) MTX, Infliximab www.indiandentalacademy.com
    • 38. Constipation   Stool: 70-85% water (100ml/d) Normal stool frequency ≥ 3/week Causes     Dietary (fibre), drugs, hormonal disturbances, neurogenic disorders systemic illnesses, IBS colonic motility disorder of defecation or evacuation (outlet) Management Diet, fluid, fibre rich diet  Avoidance of constipating drugs Only then consider medication (haemorrhoids, exacerbation of angina from straining…)  www.indiandentalacademy.com
    • 39. Laxatives        Bulk-forming Stimulant Faecal softeners Osmotic laxatives Bowel cleansing solutions Oral Rectal-suppositories, enemas General Contraindications: intestinal perforation and obstruction www.indiandentalacademy.com
    • 40. Bulk-forming laxatives      Increase faecal mass which stimulates peristalsis Bulk/softness/hydration dependant on fibre Ensure adequate fluid intake (obstruction) Effect can be delayed by a few days Try dietary fibre first!        Wheat bran, oat bran, bran buiscuits Pectins/hemicellulose (fruits, vegetables) Ispaghula (Fybogel, Isogel) Methylcellulose (Cevelac) Sterculia (Normacol) Contraindication: intestinal obstruction, colonic atony, faecal impaction Side effects: flatulence, abdominal distension, GI obstruction, rarely hypersensitivity www.indiandentalacademy.com
    • 41. Stimulant Laxatives  Increase intestinal motility Diphenylmethane derivatives  Sodium picosulfate, hydrolyzed by bacteria to active form, effects vary  Bisacodyl (Dulco-lax), usually 5-10mg nocte Anthraquinone Laxatives  Require activation in colon (bacteria), onset of action delayed (6-12 hours)  Senna (Senokot), plant derivative  Danthron (Co-danthramer) possibly carcinogenic, only use in terminally ill Docusate Sodium stimulant and softening Glycerol suppositories (Parasympathomimetics such as bethanechol, neostimin rarely used) Side effects: cramps, diarrhoea, hypokalaemia www.indiandentalacademy.com
    • 42. Osmotic laxatives Osmotically mediated water retention  Nondigestible sugars and alcohols         synthetic disaccharide, resists intestinal disacharidase draw water in osmotically, not absorbed Lactulose Use: elderly, opioids, hepatic encephalopathy (↓ ammonia production) Magnesium salts Phosphates (rectal, Fleet) Sodium citrate (rectal, Micralax Micro-enema) Polyethylene Glycol-Electrolyte Solutions - Macrogels   Sequester fluid in bowel, poorly absorbed Movicol www.indiandentalacademy.com
    • 43. Faecal softeners - Emollients  Sodium docusate (stimulant and softening)  Arachis oil enema for impacted faeces  Liquid Paraffin (oral solution) Side effects: anal irritation, interference with absorption of fat soluble vitamins, granulomatous reactions www.indiandentalacademy.com
    • 44. Bowel cleansing solutions  Before colonic surgery, colonoscopy and radiological examinations  eg Fleet, Klean-Prep, Picolax  Contraindications: obstruction, GI-ulceration, perforation, CCF, toxic colitis or megacolon, ileus  Side effects: nausea, bloating, cramps, vomiting www.indiandentalacademy.com
    • 45. Diarrhoea Definition  Excessive fluid weight (200g/day) Mechanism      Increased osmotic load Excessive secretion (electrolytes and water) Exudation of protein and fluid Altered motility (rapid transit) Often combined Management  Rehydration, maintain fluid and electrolyte balance  NaCl absorption linked with glucose uptake (rehydr. solutions)  Antimicrobial therapy. May mask clinical picture, delay clearance of organism, increase risk of systemic invasion. www.indiandentalacademy.com
    • 46. Antimotility drugs Opioids   Loperamide – Imodium         μ (motility) and δ (secretion) receptors, absorption (both) 40-50x more potent than morphine Poor CNS penetration Increases transit time and sphincter tone Antisecretory against cholera toxin and some E.coli toxin T½ 11 hours, dose: 4 mg followed by 2mg doses (16mg/d max) Overdose: paralytic ileus, CNS depression Caution in IBD (toxic megacolon) Codeine phosphate Other   Bismuth subsalicylate Adsorbents such as Kaolin (not recommended), charcoal (insufficient data for adsorbents) www.indiandentalacademy.com
    • 47. Diarrhoea Clostridium difficile  Clinical suspicion, test for toxins (stool)  Metronidazole PO  Vancomycin PO www.indiandentalacademy.com
    • 48. Irritable bowel syndrome    Recurrent abdominal pain with disturbed bowel habits 9-12% of population affected ? Pathophysiology Treatment  Dietary modification  Psychological therapies  Fibre – binding water (diarrhoea and constipation)  Antispasmodics       Anticholinergic – Hyoscyamine, methscopolamine Calcium channel antagonists and peripheral opioid receptor antagonists Mebeverine: direct effect on smooth muscle cell Tricyclic antidepressants Analgesic and neuromodulatory properties Loperamide, codeine www.indiandentalacademy.com
    • 49. Antispasmodics  Antimuscarinics  Reduce motility  Quaternary amines  eg hyoscine butylbromide (Buscopan) less lipid soluble and thus less well absorbed than atropine CI: angle-closure-glaucoma, mysthenia, paralytic ileus, pyloric stenosis and prostatic enlargement  SE: constipation, transient bradycardia, reduced bronchial secretions, urinary urgency etc Other        Direct relaxants of intestinal smooth muscle No serious side effects but avoid in paralytic ileus Alverine Mebeverine Peppermint oil (Colpermin) www.indiandentalacademy.com
    • 50. Pancreatitis Causes (mc) gallstones alcohol Diagnosis symptoms (abdominal pain, N&V) pancreas enzymes (amylase, lipase) USS +/- CT abdo severity scores (APACHE) Treatment rescuscitation (fluids + oxygen) symptomatic control (analgesia) prophylactic antibiotics if significant necrosis (30%) ?enteral nutritition chronic pancreatitis: pancreatin eg Creon www.indiandentalacademy.com
    • 51. Liver and Drugs  First pass metabolism in some drugs  Hepatic biotransformation  Phase I: oxidation, reduction, hydrolysis      Cytochrome P-450 system Note: enzyme induction by eg rifampicin, carbamazepine, phenobarbitone, alcohol Phase II: conjugation to glucoronide, sulphate, glutathion, usually resulting in inactive compounds Decrease lipid solubility and facilitate renal excretion Export into plasma or bile -> excretion via GI tract or kidney  Enterohepatic circulation (digoxin, morphine, …)  Most drugs lipophilic and thus crossing intestinal membranes www.indiandentalacademy.com
    • 52. Drug induced hepatotoxicity   50% of causes of acute liver failure Diagnosis      History Anorexia, nausea, fatigue Jaundice Blood tests Rule out other causes (viral, alcohol…) Overall rare Importance of postmarketing surveillance to detect liver toxicity www.indiandentalacademy.com
    • 53. Liver Injury and Its Patterns Navarro, V. J. et al. N Engl J Med 2006;354:731-739 www.indiandentalacademy.com
    • 54. Key Guidelines in the Recognition and Prevention of Hepatotoxicity in Clinical Practice Navarro, V. J. et al. N Engl J Med 2006;354:731-739 www.indiandentalacademy.com
    • 55. Diagnosis of Drug-Related Hepatotoxicity Navarro, V. J. et al. N Engl J Med 2006;354:731-739 www.indiandentalacademy.com
    • 56. Key Elements of and Caveats in Assessing Cause in the Diagnosis of Drug-Related Hepatotoxicity Navarro, V. J. et al. N Engl J Med 2006;354:731-739 www.indiandentalacademy.com
    • 57. Factors Predictive of a Sustained Beneficial Response to Interferon Alfa in Patients with Chronic Hepatitis Hoofnagle, J. H. et al. N Engl J Med 1997;336:347-356 www.indiandentalacademy.com
    • 58. References/further reading       BNF Harrison‘s Principles of Internal Medicine Pharmacology textbooks eg. Goodman&Gilman‘s Nice Guidelines Guidelines of the British Society of Gastroenterology Review articles (NEJM, Lancet…) www.indiandentalacademy.com
    • 59. Additional slides www.indiandentalacademy.com
    • 60. Flow chart for Mx of GU Gastric ulcer Entry or final state Action Action and outcome Stop NSAIDs, if used1 Full-dose PPI for 2 months H. pylori positive, ulcer associated with NSAID use Test for H. pylori 2 Full-dose PPI for 1 or 2 months H. pylori  negative H. pylori positive, ulcer not associated with NSAID use Eradication therapy3 H. pylori positive Endoscopy and H. pylori test4 Ulcer healed, H. pylori negative Low-dose treatment as required5 Healed Ulcer not healed, H. pylori negative Endoscopy4 Not healed Periodic review6 Refer to specialist secondary care Return to self care www.indiandentalacademy.com Refer to specialist secondary care
    • 61. Flow chart for Mx of DU Duodenal ulcer Entry or final state Action Action and outcome Stop NSAIDs, if used1 Full-dose PPI for 2 months Test positive, ulcer associated with NSAID use Test for H. pylori2 Test negative Test positive, ulcer not associated with NSAID use Response Eradication therapy3 No response or relapse Re-test for   H. pylori4 Response Negative Positive Eradication therapy5 Response Return to self care Full-dose PPI for 1 or 2 months No response No response or relapse Low-dose treatment as required6 No response Response Review8 www.indiandentalacademy.com Exclude other causes of DU 7
    • 62. Characteristics of Hepatitis A Virus, Hepatitis B Virus, and Hepatitis C Virus Lauer, G. M. et al. N Engl J Med 2001;345:41-52 www.indiandentalacademy.com
    • 63. The Replication Cycle of HBV Ganem, D. et al. N Engl J Med 2004;350:1118-1129 www.indiandentalacademy.com
    • 64. The Natural History of HCV Infection and Its Variability from Person to Person Lauer, G. M. et al. N Engl J Med 2001;345:41-52 www.indiandentalacademy.com
    • 65. Side Effects of Treatment with Interferon Alfa and Ribavirin Lauer, G. M. et al. N Engl J Med 2001;345:41-52 www.indiandentalacademy.com
    • 66. Pathogen-Host Interactions in the Pathogenesis of Helicobacter pylori Infection Suerbaum, S. et al. N Engl J Med 2002;347:1175-1186 www.indiandentalacademy.com
    • 67. Thank you For more details please visit www.indiandentalacademy.com www.indiandentalacademy.com

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