Ex.6 PUD (64)

Question 1

Peptic Ulcer Disease

Answer 1

Large Ulcers (greater than or equal to 5 mm) and extend deeper into the muscularis mucosa
-Types of ulcers: gastric, duodenal

Question 2

Epidemiology

Answer 2

-Lifetime prevalence is between 5-10% in the US
-H. Pylori prevalence is 30-40%
-PUD is prevalent among 30-50% of chronic NSAID users

Question 3

Contributing Factors

Answer 3

H. Pylori infection
NSAID use
Gastric acid + Pepsin
Cigarette smoking
Critical illness
Dietary Factors

Question 4

Pathophysiology

Answer 4

Aggressive factors (gastric acid and pepsin) overcome protective factors (mucosal defense and repair)

Question 5

Life threatening Complications:

Answer 5

GI Bleed
GI Perforation
GI obstruction

Question 6

Signs and symptoms

Answer 6

Epigastric pain
Nausea
Belching, heartburn
Bloating, Abdominal fullness
Weight loss
Early satiety

Question 7

Goals of Care

Answer 7

Relieve ulcer symptoms
Heal the ulcer
Prevent recurrence and complications
Eradicate or withdrawal of offending agent

Question 8

Non-Pharmacologic Therapy

Answer 8

Stress reduction
Smoking cessation
Avoid food and drink triggers
Avoid NSAIDs
Surgery

Question 9

H. Pylori induced Pathophysiology + Diagnosis

Answer 9

Pathophysiology
-Bacteria bind to the epithelial wall and colonize gastric acid
-Gastric acid damages tissue and leads to ulcer

Diagnosis:
-endoscopy
-Antibody detect
-Urea breath test
-Fecal antigen

Question 10

Principles of H. Pylori Tx

Answer 10

Several different tx. regimen options

Typically consists of acid suppressor + 2-3 antibiotics

Helpful to determine if patient has had any recent antibiotic exposure to predict resistance

Question 11

Therapy Overview

Answer 11

Bismuth
-Quad therapy

Clarithromycin:
-Triple therapy
-Concomitant therapy
-Sequential therapy
-Hybrid therapy

Levofloxacin
-Triple therapy
-Quad therapy (LOAD)
-Sequential therapy

Rifabutin
-Triple therapy

Vonoprazan
-Dual therapy
-Triple therapy

Question 12

Bismuth - Quad therapy

Answer 12

Bismuth salts
-Topical bactericidal effect by inhibiting aggressive factors and increasing protective factors

AVOID salicyclate products in children <12 years old due to risk of Reye’s syndrome

Contains:
1. PPI BID
2. Bismuth subsalicyclate 525mg QID
3. Metronidazole 250-500mg QID
4. Tetracycline 500mg QID
10-14 days
PREFERRED REGIMEN

Question 13

Convenience packaging for H. Pylori - Helidac

Answer 13

Helidac
-Daily admin package
-“Bismuth quadruple”
-14 blister cards containing:

-Metronidazole 250mg (i tab QID)
-Tetracycline 500mg (1 tab QID)
-Bismuth subsalicyclate 262.4mg (2 tabs QID)
-Must also take PPI BID

Question 14

Convenience packaging for H Pylori - Pylera

Answer 14

3-in-1 capsule containing:
-Bismuth subcitrate potassium 140mg
-Metronidazole 125mg
-Tetracycline 125 mg

Dose: 3 caps QID for 10 days
Must also take PPI BID
Bismuth quadruple

Question 15

Therapy overview: Clarithromycin Triple therapy and concomitant therapy

Answer 15

Triple:
1. PPI BID
2. Clarithromycin 500mg BID
3. Amoxicillin 1G BID OR Metronidazole 500mg BID
*14 days
Note: Triple therapy is no longer recommended in the US due to macrolide resistance

Concomitant:
1. PPI BId
2. Clarithromycin 250-500mg BID
3. Amoxicillin 1G BID
4. Metronidazole 250-500mg BID
*10-14 days

Note: Concomitant or “Non-Bismuth Quad” is also another first line therapy

Question 16

Clarithromycin Sequential and hybrid Therapy

Answer 16

Sequential:
1. PPI BID (days 1-10)
2. Amoxicillin 1G BID (days 1-5)
3. Metronidazole 250-500mg BID (days 6-10)
4. Clarithromycin 250-500mg BID (days 6-10)
*10 days

Hybrid:
1. PPI BID (days 1-14)
2. Amoxicillin 1G BID (days 1-14)
3. Metronidazole 250-500mg BID (days 7-14)
4. Clarithromycin 350-500mg BID (days 7-14)
*14 days

Question 17

Levofloxacin therapies

Answer 17

Triple Therapy
1. PPI BID
2. Levo 500mg daily
3. Amoxil 1G BID
*10-14 days

Quad therapy (LOAD)
1.Levo 250mg daily
2. Omeprazole (or other PPI) at high dose once daily
3. Nitazoxandine 500mg BID
4. Doxycycline 100mg Daily
*7-10 days

Sequential
1. PPI BID (days 1-10)
2. Amoxil 1G BID (days 1-5)
3. Levo 500mg daily (days 6-10)
4. Metro 500mg BID (days 6-10)
*10 days

Question 18

Rfabutin - Triple Therapy

Answer 18

1. Omeprazole 40mg Q8H
2. Amoxil 1G Q8h
3. Rifabutin 50mg 18H
   *14 days

No determined place in therapy, typically used as a salvage therapy currently

Question 19

Vonoprazan therapy

Answer 19

Potassium-Competitive Acid Blocker
-Inhibits H/K ATPase in parietal cells via competitive antagonist of potassium
Onset
2-3 hours
Indications
PUD and Erosive GERD

Question 20

Vonoprazan Dual and triple therapy

Answer 20

Dual:
1. Vono 20mg BID
2. Amoxil 1G Q8H
*14 days

Triple:
1. Vono 20mg BID
2. Amoxil 1G BID
3. Clarithromycin 500mg BID
*14 days

Question 21

Importance of PPIs in H. Pylori

Answer 21

BID PPIs are the backbone of tx

Antisecretory effects from PPIs enhance antibiotic activity
-PPIs have been shown to produce higher eradication rates

-H2RAs should not be used unless patient cannot tolerate PPI

PPIs usually not necessary beyond 2 weeks of use for eradication

Decrease in acidity, increase in antibiotic concentration

Question 22

PPI dosing H pylori

Answer 22

Omeprazole(Prilosec):
20mg

Pantoprazole (Protonix):
40mg

Esomeprazole (Nexium):
20-40mg

Lansoprazole (Prevacid)
30mg

Question 23

Probiotics

Answer 23

Could potentially be used as prophylaxis for H. Pylori colonization

Can be taken to supplement antibiotic therapy to increase eradication rates when compared to placebo
-May also reduce adverse effects of therapy

Question 24

Adverse effects probiotics

Answer 24

Metronidazole
-Avoid alcohol due to disulfiram-like rxn

Clarithromycin
-GI upset (N/V/D)

Tetracycline
-Photosensitivity
-Avoid use in children

Bismuth Salts
-Darkening of stool and tongue

Question 25

Treatment considerations: Probiotics

Answer 25

Avoid antibiotics the patient has already taken Patient adherence Consider allergies + intolerances

Question 26

Factors that predict treatment outcomes

Answer 26

Antibiotic resistance Poor medication adherence Short duration of therapy High bacterial load

Question 27

Treatment Failure

Answer 27

Confirmed by diagnostic **test 4 weeks after completion of antibiotics and after PPI has been d/c for 2 weeks** Patients who failed tx should: -Be referred to gastroenterologist -Perform a penicillin skin test if allergy previously listed

Question 28

Treatment failure: selecting salvage therapy

Answer 28

Chose antibiotics that were not used in previous regimen Reference local or institution specific resistance rates Use an extended tx. duration of 10-14 days

Question 29

NSAID Induced PUD pathophysiology

Answer 29

Rule out H. Pylori and confirm with -Endoscopy -Low Hgb and Hct if ulcers are bleeding

Question 30

Patients at diff levels of risk for NSAID GI toxicity

Answer 30

**High Risk** -History of a previously complicated ulcer, especially recent -Multiple (>2) risk factors **Moderate risk (1-2 factors)** -Age >65 years -High dose NSAID therapy -A previous hx of uncomplicated ulcer -Concurrent use of aspirin (including low dose) corticosteroids or anticoagulants **Low risk** -No risk factors

Question 31

Prevention of NSAID induced PUD

Answer 31

PPI H2RA Misoprostol COX-2 Inhibitor (admin with NSAID)

Question 32

Misoprostol (Cytotec)

Answer 32

Dosing: 200mcg QID with food MOA: -Prostaglandin E1 analog -Increased mucus and bicarbonate secretion -Increased surface active phospholipids -Increased gastric mucosal blood flow inhibits acid secretion SE: N/V/D, abdominal cramping, flatulence, HA **BOXED WARNING** -Pregnancy category X: induces labor or abortion -MUST CONFIRM patient is not pregnant in women of child-bearing age

Question 33

Celecoxib (Celebrex)

Answer 33

MOA: selective inhibition of COX-2 Equivalent anti-inflammatory effects but preserves prostaglandins **BOXED WARNING** Increased risk of CV events Naproxen is the preferred non-selective agent due to decreased CV risk

Question 34

Treatment: Sucralfate (Carafate)

Answer 34

Dosing: 1g QID before meals and at bedtime **MOA**: sucrose-sulfate-aluminum complex that interacts with albumin and fibrinogen to form a physical barrier over an open ulcer -> protects ulcer to allow it to heal SE: Constipation, metallic taste, aluminum toxicity in chronic renal failure Counseling: -Admin on empty stomach 2 hours before or 4 hours after other medications

Question 34

Tx of NSAID induced PUD

Answer 34

If patient can stop NSAID: -PPI, H2RA or sucralfate for **8 weeks** If patient is continuing NSAID: -PPI for **12 weeks** -Use lowest effective dose NSAID -May consider continuing PPI