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Pharmacotherapy of peptic ulcer

Pharmacotherapy of peptic ulcer. Dyspepsia. The term is used by different authors to mean different things ( mainly ): Non-ulcer dyspepsia GORD ( gastro-oesophageal reflux ) Gastritis Duodenal ulcers Gastric ulcers Extremely common condition Modestly higher in women than men.

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Pharmacotherapy of peptic ulcer

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  1. Pharmacotherapy of peptic ulcer

  2. Dyspepsia • The term isused by differentauthors to meandifferentthings (mainly): • Non-ulcerdyspepsia • GORD (gastro-oesophagealreflux) • Gastritis • Duodenalulcers • Gastriculcers • Extremelycommoncondition • Modestlyhigher in womenthanmen

  3. Dyspepsia - aetiology • GORD: decreased muscle tone + lower oesophageal sphincter incompetence (medicines, overeating) • Gastritis: increased acid production (H. pylori infection, acute alcohol indigestion) • Duodenal and gastric ulceration (H. pylori, medicines) • Non-ulcer dyspepsia (no specific cause can be found)

  4. Dyspepsia – clinical features • Aching above the umbillicus associated with belching • Bloating • Flatulence • Feeling of fullness • Nausea, vomiting • Heartburn (GORD)

  5. Dyspepsia – causes • Most-likely: non-ulcer dyspepsia • Unlikely: medicines, peptic ulcers, irritable bowel syndrome • Very unlikely: gastric and oesophageal cancers, atypical angina

  6. Dyspepsia – peptic ulceration • Probably the main consideration at patient with dyspepsia • Most commonly in patients aged 30 – 50 years • Typically well localised mid-epigastric pain („constant, annoying, gnawing, boring“) • Gastric ulcer: empty stomach, pain usually 30 minutes after eating, relieved by antacids or food, aggravated by alcohol and coffeine, weight loss, GI bleeding, NSAIDs • Duodenal ulcer: pain 2 to 3 hours after eating, pain that wakes person, less common GI bleeding

  7. Dyspepsia – pharmacons • Aspirin, NSAIDs very often • Antibiotics, metronidazole • ACEI, calcium channel blockers, nitrates • Alcohol • Bisphosphonates, iron, potassium supplements • Metformin, oestrogens, steroids • SSRIs, sibutramine • Theophylline

  8. Dyspepsia – irritable bowel syndrom • Patientsyoungerthan 45 • Uncomplicateddyspepsia, alsolowerabdominalpain (leftlowerquadrant), alteredbowelhabits • Alsodietaryadvice: • Haveregularmeals • Drink enough fluid • Reduceintakeofcaffeine, alcohol, fizzydrinks • Limit intakeofhighfibrefood • Reduceintakeofprocessed or re-cookedfoods • Limit freshfruitportions to 3/day

  9. Dyspepsia – gastric + oesophageal carcinoma • GI malignancies: 1st most common: colorectal carcinoma 2nd most common: pancreatic carcinoma 3rd most common: gastric carcinoma (however a rare condition) Oesophageal carcinoma (in early stages might go unnoticed, later: difficulty in swallowing, sensetion of food sticking in the oesophagus)

  10. Dyspepsia – atypical angina • Typical angina: pain in the retrosternal area with radiation to the neck, back or left shoulder that is precipitated by temperature changes or exercise • Dyspepsia-like symptoms (after heavy meal); antacids fail to relieve symptoms

  11. Dyspepsia – treatment • Lifestyle changes (lower fat diet, reduce alcohol and caffeine intake, smoking cessation, decrease weight, reduce spicy, fatty food and chocolate) • treatment options (H2 antagonists, PPIs, alginates, antacids, antibiotics)

  12. Peptic ulcer • defects of mucosa of the stomach / duodenum = mucosal damage through the lamina muscularis mucosae Clinical presentation: stomach – pain in the epigastrium shortly after meal (the patient often looses weight), nausea, anorexia duodenum – pain later after meal (fasting), often during the night, gets better after eating, the patient can gain weight

  13. Etiopatogenesis imbalance: aggressive factors ↔ protective factors mostly- HCl, pepsin production ↑ - histamine, acetylcholine, gastrin, etc. mostly- mucus, bicarbonate, fast regeneration of the mucosa, adequate perfusion of the gastric wall protective factors ↑ - mostly the production of prostaglandins by cyklooxygenase

  14. Etiopatogenesis - causes • 1st most common: Helicobacter pylori (Hp) • 2nd most common: drugs - most frequently NSAIDs, then corticoids etc. • smoking • dietary mistakes (questionable) • psychosocial stress • genetical factors • conditions with shock, burns, head traumas • Zollinger- Ellison sy. • ..........

  15. H. pylori • H. pylori enters the body through the mouth • Spiral-shaped bacterium uses its tail-like flagella to move around and get into the stomach lining, which causes inflammation • Unlike other bacteria, H. pylori bacteria can survive in the acidic environment of the stomach because they produce ureasea that neutralizes stomach acid • Urease, reacts with urea to form ammonia, which is toxic to human cells • Depending on where the infection occurs in the stomach, H. pylori can also cause overproduction of stomach acid

  16. Diagnosis and Nonpharmacologictreatment • ezophagogastroduodenoscopia histologic check of nature of the ulcer lesions presence of Hp= microscopyhisto-morfology rapid urease testbreath test testing of Ab (in plasma and in stool) • nonpharmacol. therapy: lifestyle (sleep, ↓ stress)diet (often in smaller amounts, ↓ spicy, ↓ caffeine) high fibre diet rich in vegetables and fruits no smoking, no alcohol

  17. Peptic ulcer in the stomach

  18. Peptic ulcer in the duodenum

  19. Peptic ulcer in the duodenum

  20. Helicobacterpylori – blackbacteria on thesurfaceofthegastricmucosa

  21. Pharmacotherapyofpepticulcer

  22. Antisecretorydrugs (↓ productionofHCl): protonpumpinhibitors(PPI)- omeprazole H2 receptor antagonists- famotidine anticholinergics (Pslytics)- pirenzepine DrugsneutralisingHCl: coloidalantacids- compoundsofAl a Mg reactiveantacids- NaHCO3 a CaCO3 Mucoprotectives: prostaglandines, sucralfate, compoundsofbismuth ATBs: amoxicillin, claritromycin, metronidazole, doxycycline; in caseoffailureoftherapy- levofloxacin, rifabutin

  23. Antisecretory drugs(↓ production of HCl)

  24. Exocrine Secretory Cells in the Stomach ParietalCells ChiefCells produce HCl after stimulation withgastrin, histamine and acetylcholine secrete digestive enzymes the main enzyme secreted by chief cells is pepsin pepsin is secreted as an inactive enzyme pepsinogen pepsinogen becomes active when it encounters an acidic environment and is cut apart

  25. Proton pump inhibitors • MA – irreversible blockade of H/K-ATPase(proton pump) • most effective antisecretory drugs (inhibit the last phase of HCl secretion → effect independent from the stimulus for HCl secretion) • elevated pH in the stomach decreases the conversion - pepsinogen → pepsin • “prodrugs“ - converted into active metabolite in the parietal cells of gastric mucosa • good safety profile, good tolerance • basic pharmacotherapy for peptic ulcer

  26. Proton pump inhibitors omeprazole:nearlycompleteblockadeofHClsecretionat rest and afterstimulus, hightherapeuticeffectivity druginteractions: diazepam, phenytoin, warfarinclopidogrel??- somestudies- might ↓ effectivityofclopidogrelbecauseofinhibitionof CYP450- administerratherpantoprazole pantoprazole, lanzoprazole: lessinteractions, suitable in polymorbid and olderpatientsesomeprazole:inovatedomeprazolewithfasteronset and longerdurationofactionNewerdrugs: ilaprazol tenatoprazol:strongesteffect, longestdurationofeffect

  27. H2 receptor antagonists • MA - selectiveblockadeof H2 histaminereceptors → inhibitionofhistaminemediatedHClproduction (indirecteffect on secretionmediated by Ach and gastrin) • ↓ effectivitythanprotonpumpinhibitors Examples – cimetidine, ranitidine, famotidine(more effective), nizatidine - goodsafety profile, goodtolerance - drugsof 2nd choicefortreatmentofpepticulcer; loosingtherapeutic role in most indications (↓ effectivity)

  28. Anticholinergics • MA – inhibition of M1 receptors → inhibition of acetylcholine mediated HCl production • ≈ same effectivity as H2 antagonists • ADRs – consequences of ↓activity of PS – for example dry mouth, problems with vision and urination, constipation • example- pirenzepine - they lost their therapeutic role – ADRs, ↓ effectivity than proton pump inhibitors

  29. DrugsneutralisingHCl:(antacids)

  30. coloidalantacids: ALUMINUM AND MAGNESIUMHYDROXIDE MA:weakbases → bindHCl; slightly↑ theproductionofprostaglandines ADRs: - Al hydroxide: constipation, ↓ resorptionofphosphates → osteomalacia; - Mg hydroxide: diarrhoea, hypermagnesemia; both- risk ofinteractions!! • reactiveantacids: NaHCO3and CaCO3 (sodiumhydrogencarbonate and sodiumcarbonate) MA:reactionwithHCl, duringwhich CO2 isformed ADRs: - flatulence, ´milk-alkali´ syndrome (hypercalcemia, nephrolithiasis, renalinsufficiency, ...), in thecaseof NaHCO3metabolicalkalosis!!!! Antacids – onlyforsymptomatictreatmentofdyspepsia!!!

  31. Mucoprotectives

  32. Prostaglandines • misoprostol (analog of PGE1), enprostil (analog of PGE2) - cytoprotective and mucoprotective effect - improve the microcirculation underneath the mucosa + ↑ production of mucus and bicarbonate + ↑ regenerationof defects ADRs – diarrhoea, stomach pain, abortion, - can be used in prevention of peptic ulcer formation during NSAID treatment (for that, we have other, in most cases better alternatives)

  33. Sucralfate • salt of sulfonated sucrose • MA: in an acidic environment it forms a protective layer on the surface of the mucus membrane and on the surface of the defect • probably stimulates the formation of prostaglandines • well tolerated • !don´t administer after administration of antisecretory drugs! • seldomly used

  34. Bismuth • ↑secretionofmucus and bicarbonate, ↓ secretionofHCl, antibacterialeffect • ADRs – metallic taste in themouth, blacktongue and stool, !neurotoxicity (confusion, hallucinations...) nowadaysusedlessfrequently (risk ofADRs), part of 2nd lineof H. pylorieradicationtherapy

  35. Eradication of Helicobacter pylori (needed for long-term success of pharmacotherapy of peptic ulcer in Hp positive patients)

  36. 1st linetreatment: triple therapy 7 or14 daytreatment (14 days – betterresults) • protonpumpinhibitor • claritromycin • amoxicillin– if PNC allergy - metronidazole problem – decreasingeffectivityofthetreatment (fails in approximately 25-30 % of patients)

  37. 2nd linetreatment: quadrupletherapy (in caseoffailureoftripletherapy; in patientstreatedwithmacrolidesinthepast; canbeconsidered in patientswith PNC allergy) 7 or14 daytreatment (14 days – betterresults) • protonpumpinhibitor • bismuth • metronidazole • doxycycline problem – decreasingeffectivityofthetreatment – possibilityof ↓ compliance(dosingscheme) – ADRs (mostlybismuth)

  38. Non-steroidalanti-inflammatorydrugs (NSAIDs) and pepticulcer NSAIDs – one of the most widely used drug groups – in roughly 25 % of chronic users can cause erosions and ulcerations in the GIT, in 2-4 % perforation or bleeding Possibilities of prevention– proton pump inhibitors or misoprostol during NSAID treatment; use of NSAIDs selectively inhibiting COX-2 Strategy – small risk of ulcer – NSAID on its own – moderate risk of ulcer – NSAID + PPI / misoprostol – high risk of ulcer – a) administer other (non-NSAID) analgesics, b) COX-2 selectiveNSAID + PPI / misoprostol

  39. Natural Therapy of Helicobacter with Chios Mastic?

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