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    Treatment of Peptic Ulcer: Dr.M.Purna Chandra Kala Professor DCMS, Hyd

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    Godishala Purna Chandrakala
    Yes, you're right. Certain drugs can also cause peptic ulcers: - Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, aspirin, etc. by inhibiting prostaglandin synthesis which protects the gastric mucosa. - Glucocorticoids like prednisone also inhibit prostaglandin synthesis and can cause ulcers. - Cytotoxic drugs used in chemotherapy can damage the gastric mucosa and lead to ulcers. Stressful conditions can also induce ulcers, like Cushing's ulcer seen after head trauma due to increased cortisol levels, and Curling's ulcer seen after severe burns. So drugs and stress should also

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    Treatment of Peptic Ulcer: Dr.M.Purna Chandra Kala Professor DCMS, Hyd

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    Godishala Purna Chandrakala
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    Yes, you're right. Certain drugs can also cause peptic ulcers: - Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, aspirin, etc. by inhibiting prostaglandin synthesis which protects the gastric mucosa. - Glucocorticoids like prednisone also inhibit prostaglandin synthesis and can cause ulcers. - Cytotoxic drugs used in chemotherapy can damage the gastric mucosa and lead to ulcers. Stressful conditions can also induce ulcers, like Cushing's ulcer seen after head trauma due to increased cortisol levels, and Curling's ulcer seen after severe burns. So drugs and stress should also

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    PURNA

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    Yes, you're right. Certain drugs can also cause peptic ulcers: - Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, aspirin, etc. by inhibiting prostaglandin synthesis which protects the gastric mucosa. - Glucocorticoids like prednisone also inhibit prostaglandin synthesis and can cause ulcers. - Cytotoxic drugs used in chemotherapy can damage the gastric mucosa and lead to ulcers. Stressful conditions can also induce ulcers, like Cushing's ulcer seen after head trauma due to increased cortisol levels, and Curling's ulcer seen after severe burns. So drugs and stress should also

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    Download as ppt, pdf, or txt
    33 views35 pages

    Treatment of Peptic Ulcer: Dr.M.Purna Chandra Kala Professor DCMS, Hyd

    Uploaded by

    Godishala Purna Chandrakala
    Yes, you're right. Certain drugs can also cause peptic ulcers: - Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, aspirin, etc. by inhibiting prostaglandin synthesis which protects the gastric mucosa. - Glucocorticoids like prednisone also inhibit prostaglandin synthesis and can cause ulcers. - Cytotoxic drugs used in chemotherapy can damage the gastric mucosa and lead to ulcers. Stressful conditions can also induce ulcers, like Cushing's ulcer seen after head trauma due to increased cortisol levels, and Curling's ulcer seen after severe burns. So drugs and stress should also

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    Treatment of Peptic Ulcer

    Dr.M.Purna chandra kala


    Professor
    Department of Pharmacology
    DCMS,Hyd
    Misoprostol Ranitidine
    PGE2 Gastrin
    Histamine
    + _ Proglumide
    ACh _

    M3 _ H2
    Adenyl
    PGE cyclase
    + Gastrin
    + receptor + receptor

    Ca++ ATP cAMP Ca++


    + + +

    Protein Kinase
    (Activated)
    + +
    K
    K + H

    Parietal cell
    Proton pump
    _ Lumen of stomach
    Omeprazole _
    Gastric acid Antacid
    Antacids

     Weak bases that neutralise acid


     Also inhibit formation of pepsin
    (As pepsinogen converted to pepsin at acidic pH)
     Present day antacids :
    Aluminium Hydroxide
    Magnesium Hydroxide
     Not part of Physician prescribed regimen
     OTC drug for symptomatic relief of dyspepsia
    Antacids – cont…

    Duration of action :
     30 min when taken in empty stomach
     2 hrs when taken after a meal
    Side effects :
     Al3+ antacids – constipation (As they relax gastric
    smooth muscle & delay gastric emptying)
     Mg2+ antacids – Osmotic diarrhoea .
     In renal failure Al3+ antacid – Aluminium toxicity
    &
    Encephalopathy
    Antacids – Common additives

     Simethicone – Decrease surface tension ,thereby


    reduce bubble formation
    Added to prevent reflux .
     Alginates - Form a layer of foam on top of
    gastric contents & reduce reflux
     Oxethazaine – Surface anaesthetic
    Antacid - Interactions

     Adsorb drugs and form insoluble complexes


    that are not absorbed .

    Clinical importance :
    Interactions can be avoided by taking
    antacids 2 hrs before or after ingestion of other
    drugs .
    Now answer this question

     Is it rational to combine aluminium hydroxide


    and magnesium hydroxide in antacid
    preparations ?
    Answer

     Combination provides a relatively fast and


    sustained neutralising capacity .
    (Magnesium Hydroxide – Rapidly acting
    Aluminium Hydroxide - Slowly acting )

     Combination preserves normal bowel function.


    (Aluminium Hydroxide – constipation
    Magnesium hydroxide – diarrhoea )
    Histamine H2 Receptor Antagonist
     Reversible competitive inhibitors of H2 receptor

     Highly selective, No action on H1 or H3 receptors

     Very effective in inhibiting nocturnal acid


    secretion ( as it depends largely on Histamine )
     Modest impact on meal stimulated acid
    secretion (As it depends on gastrin, acetyl
    choline and histamine)
    Cimetidine Ranitidine Famotidine Nizatidine

    Bioavailability 80 50 40 >90
    Relative Potency 1 5 -10 32 5 -10
    Half life (hrs) 1.5 - 2.3 1.6 - 2.4 2.5 - 4 1.1 -1.6
    Duration of 6 8 12 8

    action (hrs)
    Inhibition of 1 0.1 0 0
    CYP 450
    Dose mg(bd) 400 150 20 150
    H2 Blockers–Side effects & Interactions

     Extremely safe drugs

     Cimetidine causes gynecomastia, galactorrhea


    (as it is antiandrogenic & increases orolactin level)
     Cimetidine inhibits CYP450 & increases conc.
    of Warfarin, Theophylline, Phenytoin, Ethanol.
    Now answer this question

     Your friend wants to take a H2 antagonist before


    he takes alcohol to avoid gastric irritation .He
    consults you .Which H2 antagonist will you ask
    him to take ?
    Answer :

    Famotidine

    Explanation :
    All H2 antagonist except famotidine inhibit
    gastric first pass metabolism of ethanol and
    increase its bioavailability .
    Proton Pump Inhibitors

     Most effective drugs in antiulcer therapy

     Irreversible inhibitor of H+ K+ ATPase

     Prodrugs requiring activation in acid environment

     Weakly basic drugs & so accumulate in canaliculi


    of parietal cell
     Activated in canaliculi & binds covalently to
    extracellular domain of H+ K+ ATPase
     Acid secretion resumes only after synthesis of
    new molecules
    Proton Pump Inhibitors

    Omeprazole 20 mg o.d.
    Esomeprazole 20 - 40 mg o.d.
    Lansoprazole 30 mg o.d.
    Pantoprazole 40 mg o.d.
    Rabeprazole 20 mg o.d.
    Poton Pump Inhibitors – Kinetics
     Given as enteric coated granules in capsule or
    enteric coated tablets
     Pantoprazole also given intravenously

     Half life – 1.5 hrs

     Since it requires acid for activation - given 1 hr


    before meals
    Other acid suppressing agents not coadministered
    Now answer this question
     It is given in the previous slides that the half life of
    proton pump inhibitors is 1.5 hours only and
    these drugs are generally given once daily. How
    this can be justified ?

     Answer :

    P.P.I - Irreversible inhibitors of H+K+ATPase


    (Hit and run drugs)
    P.P.I. – Side effects & Interactions

     Extremely safe drugs

     Causes hypergastrinemia which leads to


    carcinod tumor in rats
     But no evidence of such tumors in man

     Inhibit CYP 450 & hence metabolsim of


    warfarin, phenytoin, etc
     Pantoprazole & Rabeprazole have no significant
    interactions
    Now Answer this Question

    A patient comes to your clinic at midnight


    complaining of heart burn. You want to relieve his
    pain immediately. What drug will you choose?
    Answer :
    Antacids

    Explanation :
    Antacids neutralise the already secreted
    acid in the stomach. All other drugs act by
    stopping acid secretion and so may not relieve
    symptoms atleast for 45 min.
    Mucosal Protective Agents
    Mucosal Protective Agents

     Sucralfate

     Misoprostol

     Colloidal Bismuth compounds


    Sucralfate

     Salt of sucrose complexed to sulfated aluminium


    hydroxide
     In acidic pH polymerises to viscous gel that
    adheres to ulcer crater
     Taken on empty stomach 1 hr. before meals

     Concurrent antacids, H2 antagonist avoided

    ( as it needs acid for activation )


    Misoprostol

     PGE1 analogue

     Modest acid inhibition

     Stimulate mucus & bicarbonate secretion

     Enhance mucusal blood flow

     Approved for prevention of NSAID induced ulcer

     Diarrhoea & cramping abd. pain – 20 %

     Not so popular as P.P.I are more effective &


    better tolerated
    Colloidal Bismuth Compounds

     Coats ulcer, stimulates mucus & bicarbonate


    secretion
     Direct antimicrobial activity against H.pylori

     May cause blackening of stools & tongue

     Not used for long periods – bismuth toxicity

    Available compounds :
     Bismuth subsalicylate – in USA

     Bismuth sobcitrate – in Europe

     Bismuth dinitrate
    Now answer this question

     A pregnant lady (first trimester) comes to you


    with peptic ulcer disease. Which drug will you
    prescribe for her ?
     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 .
    Can you identify these people ?

    Nobel prize
    Medicine –
    2005

    Discovery
    of H.pylori &
    its role in
    ulcer

    Barry J Marshall J. Robin Warren


    Eradication of H.pylori
    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


    Triple Therapy – cont …
    Some other Triple Therapy Regimens are

     Bismuth subsalicylate – 2 tab qid

    Metronidazole - 250 mg qid


    Tetracycline - 500 mg qid

     Ranitidine Bismuth citrate - 400 mg bd


    Tetracycline - 500 mg bd
    Clarithromycin / Metronidazole - 500 mg bd
    Quadruple Therapy

     Given when Triple Therapy fails

     Omeprazole / Lansoprazole - 20 / 30 mg bd

    Bismuth subsalycilate - 2 tabs qid


    Metronidazole - 250 mg qid
    Tetracycline - 500 mg qid
    Now you have learnt about drugs used for
    treating peptic ulcer ? Are there any drugs that
    can cause peptic ulcer ?

    Drugs causing peptic ulcer


     Non Steroidal Anti Inflammatory Drugs
    (NSAIDs)
     Glucocorticoids

     Cytotoxic agents
     Stress induced ulceration after head trauma

    Cushing’s ulcer
     Stress induced ulceration after severe burns

    Curling’s ulcer

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