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PHAR 255 > Peptic Ulcer Disease > Flashcards

Peptic Ulcer Disease Flashcards

1
Q

What is PUD?

A

Any breach in the mucosa of the digestive tract

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2
Q

Majority of PUD are _______ or ________ ______

A

gastric; duodenal ulcers

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3
Q

PUD is caused by imbalance of aggressive and protective factors. List the aggressive factors (6, know the 2 most important)

A
  1. H. pylori*
  2. NSAIDs*
  3. Pepsin
  4. Physiologic stress
  5. Acid
  6. Ethanol
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4
Q

PUD is caused by imbalance of aggressive and protective factors. List the protective factors (5)

A
  1. Gastric mucosa
  2. HCO3
  3. Prostaglandins
  4. Mucosal blood flow
  5. Epithelial cell regeneration
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5
Q

Describe the primary mechanism by which NSAIDs predispose the mucosa to injury (NSAID-induced PUD) (2)

A
  • Decreased COX-1 actvity = decreased prostaglandins = predispose mucosa to injury
  • Dose and duration an important determinant of risk
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6
Q

In NSAID-induced PUD, ____ and ______ triggers mucosal injury

A

acid; pepsin

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7
Q

Injury to GI mucosa leads to: (4)

A
  1. Microscopic damage –> visible tissue injury
  2. Disruption of barrier function –> increased permeability of H+
  3. Slower regeneration of epithelial cells
  4. Erosions –> ulcers –> perforations
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8
Q

True or False? Low-dose ASA has no effect on PUD development

A

False - even low dose ASA inhibits prostaglandins significantly enough for gastric ulcers

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9
Q

COX-1 or COX-2 inhibitors, which has the highest risk for NSAID-induced PUD?

A

COX-1 inhibition
(COX-2 may have a protective role)

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10
Q

What are the 2 lowest risk NSAIDs when it comes to NSAID-induced PUD?

A
  1. Celecoxib
  2. Ibuprofen
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11
Q

What are the 2 highest risk NSAIDs when it comes to NSAID-induced PUD?

A
  1. Proxicam
  2. Ketorolac
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12
Q

List 3 average risk NSAIDs when it comes to NSAID-induced PUD

A
  1. ASA low dose
  2. Diclofenac
  3. Naproxen
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13
Q

Celecoxib is thought to be the safest in terms of NSAID-induced PUD. Is that completely true though? Why? (3 total)

A
  1. Long-term use >6 months shows slight risk increases
  2. Concomitant ASA or anticoagulant increases ulcer risk
  3. High doses (>400mg/d) reduces COX-2 selectivity
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14
Q

What are the criteria for high risk of NSAID GI toxicity? (primary prevention of NSAID-induced PUD) (2)

A
  1. History of complicated ulcer, especially recent
  2. Multiple (>2) risk factors (seen in the moderate chart)
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15
Q

Moderate risk of NSAID GI toxicity is having 1-2 risk factors. What are 5 potential risk factors (primary prevention of NSAID-induced PUD)?

A
  1. Older age ≥60 years, ≥70 years
  2. NSAID use: high dose or multiple agents
  3. History of uncomplicated ulcer
  4. Concurrent ASA (including low dose), corticosteroids, anticoagulants, or SSRIs
  5. History of CVD
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16
Q

What are the 4 pathogenic mechanisms by which H. pylori induced PUD occurs?

A
  1. Direct cytotoxic effect of bacteria
  2. Renders underlying mucosa more vulnerable to acid damage
  3. High levels of ammonia:
    - Prevents detection of acidity
    - Direct toxic effect on epithelial cells
  4. Promotion of cytokines and inflammation
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17
Q

H. pylori is responsible for most duodenal and gastric ulcers. It is also a common cause of: (3)

A
  1. Chronic gastritis
  2. Gastric cancer
  3. Mucosal-associated lymphoma tissue
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18
Q

True or False. Most peptic ulcers are asymptomatic

A

True - 70%

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19
Q

What symptoms in relation to food are seen in a duodenal ulcer?

A

Food initially relieves pain, then pain 2-5 hours after a meal and at night

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20
Q

What symptoms in relation to food are seen in a gastric ulcer?

A

Immediately worsened by food

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21
Q

List 5 complications of PUD

A
  1. QoL decrease
  2. GI bleeds
  3. Perforations or fistulation
  4. Gastric outlet obstructions
  5. Mortality increases
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22
Q

If there is a GI bleed in PUD, what are some symptoms that might be seen? (5)

A
  1. N/V
  2. Hematemesis (vomit blood)
  3. Melena (black stool)
  4. Orthostatic hypotension
  5. Red blood in stool if massive bleed (hematochezia)
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23
Q

If there is a gastric outlet obstruction in PUD, what are some symptoms that might be seen? (5)

A
  1. N/V
  2. Early satiety
  3. Bloating
  4. Indigestion
  5. Anorexia and weight loss
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24
Q

If perforation or fistula occurs in PUD, what are some symptoms that might be seen? (4)

A
  1. Sudden change in symptom pattern
  2. Halitosis (bad breath)
  3. Post-prandial diarrhea
  4. Weight loss
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25
Q

The gold standard for diagnosis of PUD is?

A

Endoscopy

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26
Q

When is endoscopy indicated? (4)

A
  1. New onset symptoms (other than reflux/heartburn) >50 (>60) or red flag symptoms
  2. Any alarm features
  3. Refractory GERD
  4. At risk for Barrett’s esophagus
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27
Q

When might someone be indicated for H. pylori testing? (6 - know 2 most important)

A
  1. Active or past history of PUD*
  2. History of H. pylori infection and recurrent symptoms*
  3. Uninvestigated dyspepsia if symptoms other than GERD or no NSAID use
    - Alternatively: uninvestigated dyspepsia with any symptoms
  4. Unexplained iron deficiency
  5. Ongoing dyspeptic symptoms despite PPI use
  6. Potentially if considering chronic NSAID use (including ASA)
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28
Q

What are the 4 methods of H. pylori testing?

A
  1. Endoscopy
    - Biopsy urease
    - Histology
    - Bacterial culture
  2. Urea Breath Testing
  3. Stool Antigen Assay
  4. Serology
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29
Q

Prior to testing for H. pylori what must be done in regards to certain medications?

A

Must ds/c PPIs x 2 weeks; bismuth and antibiotics x 4 weeks as these can cause false negatives

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30
Q

What are the goals of therapy for PUD? (5)

A
  1. Relieve dyspepsia
  2. Heal the ulcer
  3. Prevent complications
  4. Prevent recurrence
  5. Implement lifestyle changes
    - Avoid foods that trigger symptoms
    - Eliminate alcohol intake
    - Smoking cessation
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31
Q

What are the 4 steps of treatment of an NSAID-induced ulcer?

A
  1. Ds/c the NSAID if possible; consider alternatives
  2. Begin ulcer healing therapy
    - PPI standard dose*
    - H2RA high dose
    - Misoprostol
  3. H. pylori testing should be done
  4. Consider ongoing secondary prevention for some patients
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32
Q

How long should the following take to heal:
1. Gastric ulcer
2. Duodenal ulcer

A
  1. Gastric = 8-12 weeks
  2. Duodenal = 4-8 weeks
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33
Q

What are 4 strategies for secondary prevention of NSAID-induced PUD?

A
  1. Lower NSAID dose
  2. Switch to celecoxib
  3. Add long-term PPI
  4. Add misoprostol
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34
Q

Terry’s Therapeutic Tip:
Of the following, should know the ranking of the efficacy for these secondary strategies for NSAID-induced PUD
1. Celecoxib alone
2. NSAID + misoprostol
3. NSAID + H2RA
4. Celecoxib + PPI
5. NSAID + PPI

A

Most efficacious:
1. Celecoxib + PPI
T2. NSAID + PPI
T2. Celecoxib alone
4. NSAID + misoprostol
5. NSAID + H2RA

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35
Q

When is secondary prevention of NSAID-induced PUD indicated? (5)

A
  1. Continued NSAID use
  2. Giant ulcer (> 1 cm in diameter) and age >50 years
  3. H. pylori resistance
  4. Refractory peptic ulcer
  5. Recurrent peptic ulcer
36
Q

What are the strategies for primary prevention of NSAID-induced PUD? (5)

A
  1. Same as secondary, but misprostol = PPIs.
  2. Lower NSAID dose
  3. Switch to celecoxib
  4. Add long-term PPI
  5. Add misoprostol
37
Q

Misoprostol is a prostaglandin analogue leading to an increase in: (3)

A
  1. Gastric mucous
  2. Bicarbonate secretion
  3. Inhibition of basal and nocturnal gastric acid secretion
38
Q

What are the 2 PUD indications where misoprostol is used?

A
  1. Treatment of a duodenal ulcer
  2. Prevention of NSAID-induced ulcers (mostly primary)
39
Q

What is the dosage and administration of misoprostol in the following?
1. Duodenal ulcer healing
2. NSAID-induced ulcer prevention

A
  1. Duodenal ulcer healing: 200mcg QID for 4 – 8 weeks
  2. NSAID-induced ulcer prevention: 200mcg QID
40
Q

Common side effects of misoprostol are? (2)

A
  1. Diarrhea and abdominal pain
  2. Dyspepsia
41
Q

What is the DI seen with misoprostol?

A

Mg+ antacids enhance GI ADRs of misoprostol

42
Q

Recommendations for Prevention of NSAID complications:
Low GI risk + Low CV risk. What to give?

A

NSAID alone

43
Q

Recommendations for Prevention of NSAID complications:
Moderate GI risk + Low CV risk. What to give?

A

NSAID + PPI/misoprostol

44
Q

Recommendations for Prevention of NSAID complications:
High GI risk + Low CV risk. What to give?

A

Alternate therapy OR COX-2 inhibitor + PPI/Misoprostol

45
Q

Recommendations for Prevention of NSAID complications:
Low GI risk + High CV risk. What to give?

A

Naproxen + PPI/Misoprostol

46
Q

Recommendations for Prevention of NSAID complications:
Moderate GI risk + High CV risk. What to give?

A

Naproxen + PPI/Misoprostol

47
Q

Recommendations for Prevention of NSAID complications:
High GI risk + High CV risk. What to give?

A

Avoid NSAIDs & COX-2 inhibitors. Use alternate therapy

48
Q

What are the drugs used in H. pylori eradication regimens? (PB AMTCLR)

A

PPIs standard doses
Bismuth subsalicylate
Amoxicillin
Metronidazole
Tetracycline
Clarithromycin
Levofloxacin
Rifabutin

49
Q

What are the current first-line options for H. pylori eradication? (2)

A
  1. PBMT - bismuth quadruple therapy
    (PPI, bismuth, metronidazole, tetracycline)
  2. PAMC - non-bismuth quadruple therapy
    (PPI, amoxicillin, metronidazole, clarithromycin)
50
Q

What are the second-line options if there is treatment failure or intolerance to first-line H. pylori medication? (2)

A
  1. PAL or PABL
    - PPI, amoxicillin, levofloxacin
    - PPI, amoxicillin, bismuth, levofloxacin
  2. PBMT if not already attempted
51
Q

What is the last-line option in H. pylori eradication medication?

A

PAR
- PPI, amoxicillin, rifabutin

52
Q

What are the 4 advantages of the PBMT H. pylori regimen?

A
  1. Highly effective
  2. Overcomes resistance
  3. Preferred if penicillin allergy
  4. Similar tolerability to triple therapy
53
Q

What are the 2 disadvantages of the PBMT H. pylori regimen?

A
  1. High pill burden
  2. Metro –> alcohol
54
Q

Basically all of the therapies for H. pylori eradication last how long?

A

14 days

55
Q

How often is each medication in PBMT dosed per day?

A

P = BID
B = QID (BID may be effective too)
M = TID-QID
T = QID (may be substituted for amoxicillin 1000mg BID)

56
Q

How often is each medication in PAMC dosed per day?

A

BID for all of them

57
Q

What are the 2 advantages of the PAMC H. pylori regimen?

A
  1. Highly effective
  2. Simplified regimen
58
Q

What are the 4 disadvantages of the PAMC H. pylori regimen?

A
  1. More GI ADRs
  2. Clarithromycin resistance may impact efficacy
  3. Penicillin allergy
  4. Metro –> alcohol
59
Q

For H. pylori triple therapy, that is PAC, PMC, and PAM, how often are the medications dosed in each regimen?

A

BID for all 3 regimens

60
Q

What are the 2 advantages of H. pylori triple therapy?

A
  1. Best compliance
  2. PAC available as Hp-PAC
61
Q

What are 4 disadvantages of H. pylori triple therapy?

A
  1. High failure rates
  2. Cost if Hp-PAC used
  3. Metro –> alcohol
  4. Penicillin allergies (except PMC)
62
Q

What is the one advantage of PAL (or PABL)?

A

Important option for previous failure

63
Q

What are the 2 disadvantages of PAL (or PABL)?

A
  1. Lower eradication rates vs. first-line
  2. Penicillin allergy
64
Q

What is the daily dosing of the PAL (or PABL) medications?

A

P = BID
A = BID
B = QID
L = once daily

65
Q

What is the daily dosing of the PAR medications?

A

P = BID
A = BID
R = BID

66
Q

What are the 2 advantages of the PAR medications?

A
  1. Important options for previous failure
  2. Low resistance rates
67
Q

What are the 4 disadvantages of the PAR medications?

A
  1. Lower eradication rates vs. first-line
  2. Rifabutin expensive
  3. Myelotoxicity
  4. Use may increase rates of mycobacterium resistance
68
Q

Although it’s not used often, explain what sequential therapy for H. pylori is.

A

PA –> PMC:
PPI BID + Amoxicillin 1000mg BID for 5 days followed by –>
PPI BID + Clarithromycin 500mg BID + Metronidazole 500mg BID for 5 days

69
Q

What is the advantage of sequential therapy for H. pylori?

A

May reduce GI ADRs

70
Q

What are the 2 disadvantages of sequential therapy for H. pylori?

A
  1. Complexity
  2. High failure rates similar to triple therapy
71
Q

There are 3 considerations when it comes to choosing an H. pylori regimen.
First, follow local resistance rates if known.
Second, follow guideline recommendations
Lastly, patient factors. What are the 6 patient factors to consider?

A
  1. Allergy history
  2. Recent antibiotic use (esp. metro/clarithro)
  3. Alcohol use
  4. Drug interaction potential
  5. Adherence/pill burden
  6. Anticoagulant or antiplatelet use if considering bismuth
72
Q

What are 2 points that need to be emphasized when counseling someone taking an H. pylori drug regimen?

A
  1. Importance of adherence
  2. Expected side effects
73
Q

What are the 2 unique side effects of metronidazole?

A
  1. Metallic taste
  2. Alcohol issues
74
Q

What are the 2 unique side effects of tetracycline?

A
  1. Photosensitivity
  2. Esophagitis
75
Q

What is the unique side effect of bismuth?

A

Darkening of tongue/stool

76
Q

What are the 5 unique side effects of levofloxacin?

A
  1. CNS
  2. Peripheral neuropathy
  3. Photosensitivity
  4. Tendon rupture
  5. QT prolongation
77
Q

What are the 2 unique side effects of rifabutin?

A
  1. Urine discoloration
  2. Myelotoxicity
78
Q

Do we know the local patterns of H. pylori resistance in Saskatchewan?

A

No

79
Q

What are the Canadian guideline steps of treatment of H. pylori starting with either PAMC or PBMT? (4)

A
  1. Try PAMC or PBMT. If it fails –>
  2. Try PAL. If it fails –>
  3. Try PBMT. If it fails –>
  4. Try PAR
80
Q

What are 3 common reasons for treatment failure of H. pylori?

A
  1. Poor adherence
  2. Incorrect regimen used
  3. High local resistance
81
Q

There is a debate on whether or not confirmation of H. pylori is routinely necessary, however, it is recommended in what 4 circumstances?

A
  1. Complicated duodenal ulcer
  2. Gastric ulcer
  3. Gastric cancer
  4. Persistent symptoms
82
Q

H. pylori confirmation of eradication should be tested _ weeks after completion of therapy

A

4

83
Q

H. pylori induced ulcer: Should PPIs be used after H. pylori eradication in duodenal and gastric ulcer? If so, how long?

A
  1. Duodenal ulcer - generally not indicated…possibly 2 weeks
  2. Gastric ulcer - continue PPI for 8 weeks
    (If continuing, reduce PPI to once daily)
84
Q

Probiotics in H. pylori-induced ulcer management. Yay or nay? (3)

A
  1. Early studies show may be helpful –> efficacy and tolerability
  2. Optimal dose, strains and administrations unknown
  3. Not harmful to try
    So, yay
85
Q

Sucralfate in H. pylori-induced ulcer management. Yay or nay? (3)

A
  1. Binds to ulcers and forms a protective barrier
  2. Inferior to H. pylori eradication and PPI use
  3. Not commonly recommended
    So, nay, mostly

PHAR 255 (14 decks)

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