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Peptic ulcer defects of mucosa of the stomach / duodenum = mucosal damage through the lamina muscularis mucosae Clinical presentation: stomach – pain.

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Presentation on theme: "Peptic ulcer defects of mucosa of the stomach / duodenum = mucosal damage through the lamina muscularis mucosae Clinical presentation: stomach – pain."— Presentation transcript:

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2 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

3 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

4 Etiopatogenesis - causes Helicobacter pylori (Hp) drugs- most frequently NSAIDs, then corticoids etc. smoking dietary mistakes (questionable) psychosocial stress genetical factors conditions with shock, burns, head traumas Zollinger- Ellison sy

5 Diagnosis and Nonpharmacologic treatment ezophagogastroduodenoscopia histologic check of nature of the ulcer lesions presence of Hp = microscopy histo-morfology rapid urease test breath test testing of Ab (in plasma and in stool) nonpharmacol. therapy: lifestyle (sleep, ↓ stress) diet (often in smaller amounts, ↓ spicy, ↓ caffeine) no smoking

6 Peptic ulcer in the stomach

7 Peptic ulcer in the duodenum

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9 Helicobacter pylori – black bacteria on the surface of the gastric mucosa

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12 Pharmacotherapy of peptic ulcer

13 Antisecretory drugs (↓ production of HCl): proton pump inhibitors (PPI)- omeprazole H 2 receptor antagonists- famotidine anticholinergics (Pslytics)- pirenzepine Drugs neutralising HCl: coloidal antacids- compounds of Al a Mg reactive antacids- NaHCO 3 a CaCO 3 Mucoprotectives: prostaglandines, sucralfate, compounds of bismuth ATBs: amoxicillin, claritromycin, metronidazole, doxycycline; in case of failure of therapy- levofloxacin, rifabutin

14 Antisecretory drugs (↓ production of HCl)

15 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

16 Proton pump inhibitors omeprazole: nearly complete blockade of HCl secretion at rest and after stimulus, high therapeutic effectivity drug interactions: diazepam, phenytoin, warfarin clopidogrel??- some studies- might ↓ effectivity of clopidogrel because of inhibition of CYP450- administer rather pantoprazole pantoprazole, lanzoprazole: less interactions, suitable in polymorbid and older patients esomeprazole: inovated omeprazole with faster onset and longer duration of action Newer drugs: ilaprazol tenatoprazol: strongest effect, longest duration of effect

17 H 2 receptor antagonists -MA - selective blockade of H 2 histamine receptors → inhibition of histamine mediated HCl production (indirect effect on secretion mediated by Ach and gastrin) -↓ effectivity than proton pump inhibitors Examples – cimetidine, ranitidine, famotidine (more effective), nizatidine - good safety profile, good tolerance - drugs of 2nd choice for treatment of peptic ulcer; loosing therapeutic role in most indications (↓ effectivity)

18 Anticholinergics -MA – inhibition of M 1 receptors → inhibition of acetylcholine mediated HCl production -≈ same effectivity as H 2 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

19 Drugs neutralising HCl: (antacids)

20 coloidal antacids: aluminum and magnesium hydroxide MA: weak bases → bind HCl; slightly ↑ the production of prostaglandines ADRs: - Al hydroxide: constipation, ↓ resorption of phosphates → osteomalacia; - Mg hydroxide: diarrhoea, hypermagnesemia; both- risk of interactions!! reactive antacids: NaHCO 3 and CaCO 3 MA: reaction with HCl, during which CO 2 is formed ADRs: - flatulence, ´milk-alkali´ syndrome (hypercalcemia, nephrolithiasis, renal insufficiency,...), in the case of NaHCO 3 metabolic alkalosis !!!! Antacids – only for symptomatic treatment of dyspepsia!!!

21 Mucoprotectives

22 Prostaglandines misoprostol (analog of PGE 1 ), enprostil (analog of PGE 2 ) - 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)

23 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

24 Bismuth -↑ secretion of mucus and bicarbonate, ↓ secretion of HCl, antibacterial effect -ADRs – metallic taste in the mouth, black tongue and stool, !neurotoxicity (confusion, hallucinations...) nowadays used less frequently (risk of ADRs), part of 2nd line of H. pylori eradication therapy

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

26 1st line treatment: triple therapy 7 or14 day treatment (14 days – better results) proton pump inhibitor claritromycin amoxicillin – if PNC allergy - metronidazole problem – decreasing effectivity of the treatment (fails in approximately % of patients)

27 2nd line treatment: quadruple therapy (in case of failure of triple therapy; in patients treated with macrolides in the past; can be considered in patients with PNC allergy) 7 or14 day treatment (14 days – better results) proton pump inhibitor bismuth metronidazole doxycycline problem – decreasing effectivity of the treatment – possibility of ↓ compliance (dosing scheme) – ADRs (mostly bismuth)

28 New possibilities: sequential therapy 10 days (5 + 5), for example: First 5 days proton pump inhibitor amoxicillin Next 5 days proton pump inhibitor claritromycin tinidazole (possibly metronidazole ??)

29 Failure of the therapy: Future?? :

30 Non-steroidal anti-inflammatory drugs (NSAIDs) and peptic ulcer 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, or b) COX-2 selective NSAID + PPI / misoprostol


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