Scribd Logo
Upload

Welcome to Scribd!

  • 144 views

    Chapter 32 Supplemental

    Uploaded by

    Marry
    This document summarizes the key drugs used to treat gastric acidity, peptic ulcers, and gastroesophageal reflux disease. It describes the mechanisms of action of H2 receptor antagonists, proton pump inhibitors, prostaglandin analogs, and cytoprotective agents. It provides case studies on the treatment of GERD, H. pylori infection-induced peptic ulcers, and NSAID-induced ulcers. The document recommends proton pump inhibitors as the preferred treatment due to limitations with H2 receptor antagonists and describes combination regimens used to effectively eradicate H. pylori infections.

    Copyright:

    © All Rights Reserved
    Download as DOCX, PDF, TXT or read online from Scribd

    Chapter 32 Supplemental

    Uploaded by

    Marry
    144 views6 pages
    This document summarizes the key drugs used to treat gastric acidity, peptic ulcers, and gastroesophageal reflux disease. It describes the mechanisms of action of H2 receptor antagonists, proton pump inhibitors, prostaglandin analogs, and cytoprotective agents. It provides case studies on the treatment of GERD, H. pylori infection-induced peptic ulcers, and NSAID-induced ulcers. The document recommends proton pump inhibitors as the preferred treatment due to limitations with H2 receptor antagonists and describes combination regimens used to effectively eradicate H. pylori infections.

    Copyright

    © © All Rights Reserved

    Available Formats

    DOCX, PDF, TXT or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    This document summarizes the key drugs used to treat gastric acidity, peptic ulcers, and gastroesophageal reflux disease. It describes the mechanisms of action of H2 receptor antagonists, proton pump inhibitors, prostaglandin analogs, and cytoprotective agents. It provides case studies on the treatment of GERD, H. pylori infection-induced peptic ulcers, and NSAID-induced ulcers. The document recommends proton pump inhibitors as the preferred treatment due to limitations with H2 receptor antagonists and describes combination regimens used to effectively eradicate H. pylori infections.

    Copyright:

    © All Rights Reserved
    Download as DOCX, PDF, TXT or read online from Scribd
    Download as docx, pdf, or txt
    144 views6 pages

    Chapter 32 Supplemental

    Uploaded by

    Marry
    This document summarizes the key drugs used to treat gastric acidity, peptic ulcers, and gastroesophageal reflux disease. It describes the mechanisms of action of H2 receptor antagonists, proton pump inhibitors, prostaglandin analogs, and cytoprotective agents. It provides case studies on the treatment of GERD, H. pylori infection-induced peptic ulcers, and NSAID-induced ulcers. The document recommends proton pump inhibitors as the preferred treatment due to limitations with H2 receptor antagonists and describes combination regimens used to effectively eradicate H. pylori infections.

    Copyright:

    © All Rights Reserved
    Download as DOCX, PDF, TXT or read online from Scribd
    Download as docx, pdf, or txt
    of 6

    Workbook and Casebook for Goodman and Gilman's The Pharmacological Basis of Therapeutics >

    Chapter 32: Pharmacotherapy of Gastric Acidity, Peptic Ulcers, and Gastroesophageal


    Reflux Disease

    INTRODUCTION
    This chapter will be most useful after having a basic understanding of the material in Chapter 45, Pharmacotherapy
    of Gastric Acidity, Peptic Ulcers, and Gastroesophageal Reflux Disease in Goodman & Gilman's The Pharmacological
    Basis of Therapeutics, 12th Edition. In addition to the material presented here, the 12th Edition contains:

    A description of the physiology of gastric secretion

    Therapeutic strategies for the treatment of specific acid-peptic disorders

    Table 45-2 which shows the composition and acid neutralizing capacities of popular antacid preparations

    LEARNING OBJECTIVES

    Identify the sites in the gastric parietal cell where drugs act to suppress acid secretion.

    Describe the mechanism of action of proton pump inhibitors, H2 receptor antagonists, and
    prostaglandin analogs to suppress gastric acid secretion.

    Describe the limitations to the use of H2 receptor antagonists in chronic acid suppression.

    Identify potential drug interactions with proton pump inhibitors and H 2 receptor antagonists.

    Describe the mechanism of action of drugs that enhance gastric cytoprotection.

    Describe the recommendations for therapy of gastroesophageal reflux disease (GERD) and
    peptic ulcer disease.

    Understand the role of Helicobacter pylori infection in peptic ulcer disease and the therapeutic
    principles for its eradication.

    Describe appropriate therapy for NSAID-induced ulcers.

    DRUGS INCLUDED IN THIS CHAPTER


    Cimetidine (TAGAMET, others)
    Famotidine (PEPSID, others)
    Nizatidine (AXID, others)
    Rabeprazole (ACIPHEX)

    Dexlansoprazole (KAPIDEX)
    Lansoprazole (PREVACID)
    Omeprazole (PRILOSEC, others)
    Ranitidine (ZANTEC, others)

    Esomeprazole (NEXIUM)
    Misoprostol (CYTOTEC)
    Pantoprazole (PROTONIX)
    Sucralfate (CARAFATE, others)

    MECHANISMS OF ACTION OF DRUGS USED TO TREAT GASTRIC ACID


    DISEASES
    DRUG CLASS

    H2 Receptor
    Antagonists

    Proton Pump
    Inhibitors

    DRUGS

    MECHANISM OF ACTION

    Cimetidine
    Ranitidine
    Famotidine
    Nizatidine

    Competes with histamine for binding to H2 receptors on the


    basolateral membrane of parietal cells (see Figure 32-1)

    Lansoprazole

    The activated form binds covalently with sulfhydryl groups


    on cysteine in the H+,K+-ATPase located on the luminal
    membrane of the parietal cell to suppress acid secretion
    (see Figure 32-1)

    Pantoprazole
    Omeprazole

    Workbook and Casebook for Goodman and Gilman's The Pharmacological Basis of Therapeutics >
    DRUG CLASS

    DRUGS

    MECHANISM OF ACTION

    Esomeprazole
    Dexlansoprazole
    Rabeprazole

    Prostaglandin
    Analog
    Cytoprotective
    Agent

    Misoprostol
    Sucralfate

    Binds to the EP3 receptor on parietal cells decreasing cyclic AMP


    and gastric acid secretion (see Figure 32-1)
    Forms a viscous, sticky polymer that adheres to epithelial cells
    and ulcer craters and is cytoprotective

    Antacids

    Various over-theNeutralize gastric acid


    counter (OTC) products

    Bismuth

    Various OTC products

    Binds to the base of ulcers and promotes mucin and


    bicarbonate production

    CASE 32-1
    A 42-year-old woman is seen because of worsening heartburn during the past week. She was
    first diagnosed with GERD 1 month ago and treatment was begun with cimetidine 400 mg
    once daily. Two weeks later the cimetidinedosage was increased to 400 mg twice daily.

    a. What is the reason for the worsening of her GERD symptoms?


    Cimetidine is an H2 receptor antagonist and tolerance to acid suppressing effects of
    these drugs has been shown to develop as early as 2 to 5 days after beginning
    treatment. One mechanism for this phenomenon is secondary to the
    hypergastrinemia that stimulates histamine release and overcomes the H2 receptor
    blockade.
    b. What are the mechanisms of action of H2 receptor blockers and proton
    pump inhibitors?
    The mechanisms of action of these drugs is shown in Figure 32-1. The H2 receptor
    blockers suppress gastric acid secretion by competing with histamine for binding to
    H2 receptors on the basolateral membrane of parietal cells. The structural similarity
    of the H2 receptor antagonists and histamine is shown in Figure 32-2.
    The proton pump inhibitors are prodrugs that require activation in an acid
    environment (see Figure 32-3). The activated form binds covalently with sulfhydryl
    groups on cysteine in the H+,K+-ATPase located on the luminal membrane of the
    parietal cell. Despite the short plasma half-lives (0.5-2 h) of the parent drug, acid
    suppression continues for 24 to 48 hours or until new pump molecules are
    synthesized.

    c. What is a rational approach to her treatment?


    A rational choice would be to switch her to a proton pump inhibitor. Although these
    drugs can also cause a hypergastrinemia, it does not result in tolerance because the
    inhibition occurs at the H+,K+-ATPase which is the final step in gastric acid
    secretion. Figure 32-4 shows the general guidelines for medical management of
    GERD.

    Workbook and Casebook for Goodman and Gilman's The Pharmacological Basis of Therapeutics >

    d. If the patient is switched to a proton pump inhibitor, of what adverse


    effects should she be warned?
    Proton pump inhibitors are metabolized by hepatic CYPs and they may interfere with
    the elimination of other drugs cleared by this route. Chronic treatment with proton
    pump inhibitors decreases the absorption of vitamin B12. The loss of gastric acidity
    may affect the bioavailability of drugs, most notably iron salts. This may result in an
    iron deficiency anemia.

    FIGURE
    32-4
    General
    guidelines
    for the
    medical

    management of gastroesophageal reflux disease (GERD). Only medications that suppress


    acid production or that neutralize acid are shown.
    CASE 32-2
    A 56-year-old man is diagnosed with duodenal ulcer complicated by H. pylori infection. He
    has been treated with amoxicillin for 2 weeks, but his symptoms of stomach pain persist.

    a. Why has his therapeutic regimen not been effective? What


    problems might be the result of this therapeutic regimen?
    H. pylori, a gram negative rod, has been associated with gastritis and subsequent
    development of gastric and duodenal ulcers, gastric adenoma, and gastric B-cell

    Workbook and Casebook for Goodman and Gilman's The Pharmacological Basis of Therapeutics >

    lymphoma. Single antibiotic therapy for H. pyloriinfection is not effective for


    eradication and may result in bacterial resistance that is more difficult to treat than
    the initial infection.

    b. What would you recommend for the treatment of his condition?


    A common therapeutic approach would be to use a proton pump inhibitor
    plus clarithromycin plus eithermetronidazole or amoxicillin for 14 days. Another
    common approach would be to use a proton pump inhibitor
    plus metronidazole plus bismuth plus tetracycline.

    c. What is the most common problem observed with your


    recommended regimen?
    The most common problem observed with these therapeutic regimens is poor patient
    compliance due to the number of medications that must be taken each day and to
    medication-related side effects.
    Table 32-1 Therapy of Helicobacter pylori Infection
    Triple therapy 14
    days: Proton pump inhibitor
    + clarithromycin 500 mg
    plus metronidazole 500 mg
    oramoxicillin 1 g twice a day
    (tetracycline 500 mg can be
    substituted
    for amoxicillin or metronidazole
    )

    Quadruple therapy 14
    days: Proton pump inhibitor
    twice a day
    + metronidazole 500 mg three
    times daily
    plusbismuth subsalicylate 525
    mg + tetracycline 500 mg four
    times daily

    H2 receptor antagonist twice a


    day plus bismuth subsalicylate
    525 mg + metronidazole 250
    mg + tetracycline500 mg four
    times daily

    DOSAGES:
    Proton pump inhibitors:
    Omeprazole: 20 mg
    Lansoprazole: 30 mg
    Rabeprazole: 20 mg
    Pantoprazole: 40 mg
    Esomeprazole: 40 mg

    H2 receptor antagonists:
    Cimetidine: 400 mg
    Famotidine: 20 mg
    Nizatidine: 150 mg
    Ranitidine: 150 mg

    CASE 32-3
    A 64-year-old man is referred because of stomach pain. He has been
    diagnosed with osteoarthritis and has been taking a COX-1 inhibitor for the
    past 3 months. Workup shows that he has a duodenal ulcer that you suspect
    is a result of his NSAID use.
    a. Describe the pathogenesis of NSAID-induced ulcers.
    NSAIDs diminish prostaglandin formation by inhibiting cyclooxygenase. This effect
    can result in enhanced gastric acid secretion (prostaglandins may lower gastric acid
    secretion). In addition, prostaglandins stimulate gastric mucin production that
    provides a cytoprotective effect to the gastric mucosa which is diminished by NSAIDs.

    b. What are your therapeutic options?

    Workbook and Casebook for Goodman and Gilman's The Pharmacological Basis of Therapeutics >

    One option is to change this patient to an NSAID that is a selective inhibitor of COX-2,
    although this may not completely eliminate the risk of ulcer formation. Another
    option is to try misoprostol although it has numerous gastrointestinal side effects and
    4-times-daily dosing is inconvenient. Finally, NSAID-induced ulcers can be managed
    with acid suppression using either an H2 receptor antagonist or proton pump inhibitor.
    Proton pump inhibitors can effectively heal active ulcers and prevent recurrence in
    the setting of continued NSAID administration.

    KEY CONCEPTS

    Proton pump inhibitors are superior to H2 receptor antagonists for acid suppression in
    patients with GERD and peptic ulcers.

    Tolerance to the acid-suppressing effects of the H2 receptor antagonists is commonly


    observed and limits their continuous use.

    H. pylori is effectively eradicated with a combination of acid-suppressing drugs and


    multiple antibiotics administered for 10 to 14 days.

    NSAID-induced ulcers can be effectively treated with a proton pump inhibitor even
    during continued NSAID administration.

    SUMMARY: DRUGS USED TO TREAT GASTRIC ACIDITY, PEPTIC ULCERS, AND GASTROESOPHAGEAL REFLUX
    DISEASE

    CLASS AND
    SUBCLASSES

    H2 Receptor
    Antagonists

    NAMES

    Cimetidine
    Ranitidine

    Diarrhea,
    Promote healing headache,
    drowsiness,
    of gastric and
    duodenal ulcers, fatigue,
    muscular
    treatment of
    uncomplicated pain, and
    constipation
    GERD, and to
    prevent
    occurrence of
    Tolerance
    stress ulcers
    occurs with
    long-term use

    Same
    as cimetidine
    Same
    Nizatidine
    as cimetidine
    Treatment of
    Omeprazole gastric and
    duodenal ulcers
    Famotidine

    Proton Pump
    Inhibitors

    CLINICAL USES

    TOXICITIES
    UNIQUE;
    COMMON
    CLINICALLY
    IMPORTANT

    Same
    as cimetidine
    Same
    as cimetidine
    Nausea,
    flatulence,
    abdominal

    Inhibition of hepatic
    CYPs Delirium and
    confusion with IV use
    in elderly patients
    Gynecomastia in men
    Galactorrhea in
    women

    No inhibition of
    hepatic CYPs
    No inhibition of
    hepatic CYPs
    Metabolized by
    hepatic CYPs and may

    Workbook and Casebook for Goodman and Gilman's The Pharmacological Basis of Therapeutics >

    CLASS AND
    SUBCLASSES

    NAMES

    CLINICAL USES

    TOXICITIES
    UNIQUE;
    COMMON
    CLINICALLY
    IMPORTANT

    Esomeprazol
    e
    Lansoprazole

    and GERD

    pain,
    constipation

    Pantoprazole
    Rabeprazole

    Prostaglandin
    Misoprostol
    Analog

    Cytoprotective
    Sucralfate
    Agents

    Bismuth

    Prevention of
    NSAID-induced
    mucosal injury

    Treatment of
    peptic ulcer
    disease

    Diarrhea

    affect other drugs that


    are metabolized by
    hepatic CYPs
    Decreased absorption
    of folic acid, vitamin
    B12, and iron salts

    Clinical exacerbation
    of inflammatory bowel
    disease
    Contraindicated in
    pregnancy

    Avoid in patients with


    renal failure
    Constipation

    May inhibit the


    absorption of other
    drugs

    Treatment of
    peptic ulcer
    Bismuth subsalicylate
    particularly in
    Black tongue
    OTC products
    is associated with
    patients with H. and stools
    salicylate poisoning
    pyloriinfection
    (see Table 32-1)

    You might also like