PUD

H. pylori-positive patient with H. pylori-associated ulcer

"effective, well tolerated, easy to adhere to, and cost-effective". -Standard initial treatment for H. pylori eradication involves PPI-based three-drug regimen (aka triple therapy) for 10 to 14 days consisting of antisecretory drug (PPI) with two antibiotics (clarithromycin-amoxicillin). -some favor initial 7-day regimens, the longer the course of therapy, typically the better the H. pylori eradication results. -Medications should be taken 30-60 minutes prior to a meal. -Amoxicillin is preferred as bacterial resistance to it is virtually absent, it has fewer adverse effects -leaves metronidazole as a backup agent for second-line therapy. -two-drug regimens that combine a PPI and either amoxicillin or clarithromycin have yielded marginal and variable eradication rates in the United States and are not recommended. -use of only one antibiotic is associated with a higher rate of antimicrobial resistance

H. pylori positive patient with penicillin allergy

**Treatment failures should be referred to a gastroenterologist for further diagnostic evaluation** -patients with penicillin allergies substitute metronidazole for amoxicillin in PPI-based 3-drug therapy accordingly. -Penicillin-allergic patients may also start alternate initial treatment using a "bismuth-based quadruple therapy", consisting of a PPI or H2RA, bismuth salt, tetracycline, and metronidazole for 10-14 days. Bismuth has a sort of topical effect C. levofloxacin regimen

Proton pump inhibitors

-Headache, N/V/D, flatulence Less common: thrombocytopenia, neutropenia, hypomagnesemia, hypocalcemia, liver function abnormalities, renal impairment Well tolerated; may be associated with increased risk of fractures, pneumonia, Clostridium difficile infection

Histamine-2 receptor antagonists

-Headache, dizziness, diarrhea, somnolence, gynecomastia ( cimetidine) Less common: thrombocytopenia, neutropenia, liver function abnormalities, renal impairment, pancreatitis

bismuth 4th therapy

-PPI, two antibiotics, and a bismuth salt is also effective and employable alternate first line therapy for H. pylori positive patients. -increasing eradication rates to acceptable levels and reduce the risk of antimicrobial resistance. -**bismuth based quadruple therapy is the treatment of choice when medication costs are of upmost importance**

Sequential

-dispensing antibiotics that do not promote bacterial resistance (amoxicillin) first in hopes to decrease the bacterial load and preexisting resistant microorganisms along with a PPI for 5 days -followed by an additional set of antibiotics to kill remaining organisms (clarithromycin and tinidazole or metronidazole), plus a PPI for an additional 5 days.

H. pylori-positive patient with recurrent ulcer If a second course of treatment is required (due to failed eradication with first line therapy)... Therapy Options

1. Bismuth-based four-drug regimen with a bismuth salt, metronidazole, tetracycline, and a PPI should be used. ' -Eradication rates for bismuth-based therapies ate similar to those achieved from PPI-based triple therapy. -"Maintenance therapy with a PPI or H2RA should be limited to patients with ulcer complications and those who fail eradication" [pg 22]. 2. levofloxacin-containing regimen may be an alternative second-line eradication regimen and may be better tolerated than PPI-based quadruple therapy **clarithromycin 250-500 mg 4x daily may be substituted for tetracycline to yield similar results, but will increase chance of developing adverse effects ***don't drink alcohol with metronidazole

All second line treatments should consist of treatments with:

1.antibiotics that are not associated with resistance 2.use antibiotics that were not previously used during initial therapy 3.extended duration of treatment (14 days) 4.use a drug that has a topical effect such as bismuth

3. Describe alternative dosage forms and dosing strategies for preventing SRMB given the patient's clinical condition to achieve cost-effective care.

Antisecretory therapy (PPIs and H2RA) is preferred, however sucralfate (mucosal protectant) is also welcome. Sodium bicarbonate suspensions of PPIs may be used as alternatives to H2RAs or sucralfate (2 40 mg doses 1st day, 1 20 mg dose days thereafter). PPIs are more potent, and unlike H2RAs do not develop tolerance. For cost-effective measures, patients who can take oral medications or have a working NG tube in place should be placed on an oral or compounded PPI suspension. If patients cannot utilizes these routes, an IV H2RA may be appropriate. If patient has renal dysfunction, develops thrombocytopenia or mental changes while on an H2RA then IV PPI may be appropriate [44].

COX

COX-1: found in most body tissue; produces protective PGs that help regulate GI mucosal integrity, platelet homeostasis and renal function COX-2: undetectable in most tissues in normal homeostasis; is induced by inflammatory stimuli and produces PGs associated with inflammation, pain and fever. adverse effects of NSAIDs are primarily associated with the inhibition of COX-1, whereas anti-inflammatory actions result primarily form NSAID inhibition of COX-2

Sucralfate

Constipation

1. Formulate an appropriate pharmacotherapy treatment plan for the patient with acute peptic ulcer bleeding.

Conventional therapy may be employed, however maintenance therapy may be required to prevent ulcer recurrence [pg 29]. Blatchford risk stratification scale should be used to determine the extent of risk and determine the need for endoscopic intervention [39-41]. • Initial therapy for patients with hemostatic instability is too correct fluid volume loss with continuous sodium chloride IV infusion. • Diagnostic endoscopy should occur within 24 hrs of presentation to help determine source of bleeding, potential for re-bleeding, and possible therapeutic interventions. A minimum of 2 endoscopic exams should be employed for greater accuracy. • Patients should be tested for H. pylori at the time of endoscopy. Watch out for false-negatives. • Antisecretory therapy (PPIs) may be used as an adjuvant to endoscopic to prevent re-bleeding in high risk patients. (H2RAs are ineffective in preventing PUD re-bleeding because it does not achieve an intragastric pH of 6. Meanwhile PPIs reduce the incidence of re-bleeding and need for surgery.) ROA and dose depends on the patient and their clinical situation. Many clinicians recommend high dose continuous IV therapy of pantoprazole and esomeprazole prior to endoscopy. Patients should be switched to oral PPI upon completion of IV therapy.

Misoprostol

Diarrhea, abdominal pain, headache, nausea/vomiting, flatulence, dysmenorrhea, hypophosphatemia No preggy

3. Describe the mechanism of NSAID-induced gastric mucosal injury.

NSAID-induced ulcers are a form of chronic peptic ulcer. NSAIDS cause gastric mucosal damage via two mechanisms: 1. Direct or topical irritation of the gastric epithelium: Acidic NSAIDs, like aspirin (most-damaging), and most non-aspirin NSAIDs have topical irritant effects. They have the ability to decrease the hydrophobicity of the mucous layer of the gastric mucosa. Even NSAID prodrugs, though they may not cause direct acute topical injury, they can still case systemic inhibition of endogenous PGs (the onset of injury is typically initiated by topically the acidic nature of many NSAIDs) 2. Systemic inhibition of endogenous mucosal PG synthesis: inhibition of the protective PGs limit the ability of the mucosa to defend itself against injury. This plays a vital role in the development of a gastric ulcer

2. List the risk factors associated with stress-related mucosal bleeding (SRMB) in the critically ill patient in the intensive care setting.

SRMD usually occurs in the stomach of critically ill patients during hospitalization [pg 38-39]. Primary pathogenic factor of SRMD in critically ill patients is thought to be mucosal ischemia resulting from reduced gastric blood flow (decreased oxygen and nutrient delivery). Risk factors associated with SRMB include respiratory failure, coagulopathy, hypotension, sepsis, hepatic failure, acute renal failure, high-dose corticosteroid therapy (>250 mg/day), multiple trauma, severe burns, head injury, traumatic spinal cord injury, major surgery, prolonged ICU admission (> 7 days), and history of GI bleeding. Patients with respiratory failure, coagulopathy or two of the aforementioned risk factors should receive prophylaxis treatments [pg 41]. Keep in mind that SRMD ulcers may also occur in response to gastric hypersecretion, gastric outlet obstruction, genetic predisposition, concomitant diseases, heavy tobacco use

Treatment for patient with active ulcer, taking a nonselective NSAID

o Non-pharmacologic therapy -Dietary modifications: avoid food/beverages causing dyspepsia/exacerbated symptoms -Alternative pain-relief agents such as acetaminophen or nonacetylated salicylates -In extreme cases, possible vagotomy surgery (comes w/ complications of its own) o Pharmacologic therapy -PPIs or sucralfate are preferred, as they accelerate ulcer healing and provide more effective relief of symptoms (PPI treatment should be extended from 4 to 8-12 weeks if the NSAID must be continued *Treatment for patient at risk for ulcer-related*-Prophylactic co-therapy of PPI or misoprostol decreases ulcer risk and upper GI complications for patients taking nonselective NSAIDs

Lifestyle modifications:

reducing stress and stopping cigarette smoking are encouraged o Use COX-2 selective NSAIDS in lieu of nonselective NSAIDs to avoid inhibition of GI-protective PGs; do not use with aspirin (be mindful of any heart condition that the patient may have) Use of non-acetylated salicylates (i.e. salsalate) [pg 8] o Please look above for additional risk factors to avoid if possible o Prophylactic co-therapy of PPI or misoprostol (not recommended for pregnant patients) decreases ulcer risk and upper GI complications for patients taking nonselective NSAIDs [pg 19]

Recommend the appropriate ulcer prophylaxis or treatment for a patient taking a nonselective NSAID with an active ulcer or at risk for ulcer-related complications.

• Age >65 • Previous peptic ulcer • Previous ulcer-related upper GI complication • High-dose NSAIDs • Multiple NSAID use • Selection of NSAID (e.g., COX-1 vs. COX-2 inhibition) • NSAID-related dyspepsia • Aspirin (including cardioprotective dosages) • Concomitant use of: o NSAID plus low-dose aspirin (irreversibly inhibits platelet COX-1, ↓ platelet aggr. ,↑ bleeding times) o Oral bisphosphonates (e.g., alendronate) o Corticosteroids o Anticoagulant or coagulopathy o Antiplatelet drugs (e.g., clopidogrel) o Selective serotonin reuptake inhibitor • Chronic debilitating disorders (e.g., cardiovascular disease, rheumatoid arthritis) • Helicobacter pylori infection • Cigarette smoking • Alcohol consumption • Ulcer prophylaxis

Formulate appropriate counseling and medication adherence information to provide a patient with an H. pylori-associated ulcer on eradication therapy.

• We want to stress medication adherence to help achieve maximal response • Adjust medications in accordance to any polymorphisms patient carries • Mention Common Adverse Effects o Nausea, vomiting, abdominal pain, diarrhea, taste disturbances (metronidazole and clarithromycin) o Adverse effects with metronidazole are dose related; this drug has a reaction with alcohol o Tetracycline may cause photosensitivity; should be avoided in children due to possible tooth discoloration o Bismuth salts may cause darkening of the stool and tongue o Antibiotic-associated diarrhea, Clostridium difficile, oral thrush, vaginal candidiasis may occur • For at-risk patients or patients already on eradication therapy: they may benefit from the addition of probiotics (i.e. lactobacillus and Bifidobacterium) and foodstuffs (i.e. cranberry juice and milk proteins) with bioactive components to help proactively control H. pylori and reduce the adverse effects of PPI-based triple therapy.