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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
The gold standard for diagnosis of PUD is?
Endoscopy
26
When is endoscopy indicated? (4)
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
27
When might someone be indicated for H. pylori testing? (6 - know 2 most important)
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)
28
What are the 4 methods of H. pylori testing?
1. Endoscopy - Biopsy urease - Histology - Bacterial culture 2. Urea Breath Testing 3. Stool Antigen Assay 4. Serology
29
Prior to testing for H. pylori what must be done in regards to certain medications?
Must ds/c PPIs x 2 weeks; bismuth and antibiotics x 4 weeks as these can cause false negatives
30
What are the goals of therapy for PUD? (5)
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
31
What are the 4 steps of treatment of an NSAID-induced ulcer?
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
32
How long should the following take to heal: 1. Gastric ulcer 2. Duodenal ulcer
1. Gastric = 8-12 weeks 2. Duodenal = 4-8 weeks
33
What are 4 strategies for secondary prevention of NSAID-induced PUD?
1. Lower NSAID dose 2. Switch to celecoxib 3. Add long-term PPI 4. Add misoprostol
34
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
Most efficacious: 1. Celecoxib + PPI T2. NSAID + PPI T2. Celecoxib alone 4. NSAID + misoprostol 5. NSAID + H2RA
35
When is secondary prevention of NSAID-induced PUD indicated? (5)
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
What are the strategies for primary prevention of NSAID-induced PUD? (5)
1. Same as secondary, but misprostol = PPIs. 2. Lower NSAID dose 3. Switch to celecoxib 4. Add long-term PPI 5. Add misoprostol
37
Misoprostol is a prostaglandin analogue leading to an increase in: (3)
1. Gastric mucous 2. Bicarbonate secretion 3. Inhibition of basal and nocturnal gastric acid secretion
38
What are the 2 PUD indications where misoprostol is used?
1. Treatment of a duodenal ulcer 2. Prevention of NSAID-induced ulcers (mostly primary)
39
What is the dosage and administration of misoprostol in the following? 1. Duodenal ulcer healing 2. NSAID-induced ulcer prevention
1. Duodenal ulcer healing: 200mcg QID for 4 – 8 weeks 2. NSAID-induced ulcer prevention: 200mcg QID
40
Common side effects of misoprostol are? (2)
1. Diarrhea and abdominal pain 2. Dyspepsia
41
What is the DI seen with misoprostol?
Mg+ antacids enhance GI ADRs of misoprostol
42
Recommendations for Prevention of NSAID complications: Low GI risk + Low CV risk. What to give?
NSAID alone
43
Recommendations for Prevention of NSAID complications: Moderate GI risk + Low CV risk. What to give?
NSAID + PPI/misoprostol
44
Recommendations for Prevention of NSAID complications: High GI risk + Low CV risk. What to give?
Alternate therapy OR COX-2 inhibitor + PPI/Misoprostol
45
Recommendations for Prevention of NSAID complications: Low GI risk + High CV risk. What to give?
Naproxen + PPI/Misoprostol
46
Recommendations for Prevention of NSAID complications: Moderate GI risk + High CV risk. What to give?
Naproxen + PPI/Misoprostol
47
Recommendations for Prevention of NSAID complications: High GI risk + High CV risk. What to give?
Avoid NSAIDs & COX-2 inhibitors. Use alternate therapy
48
What are the drugs used in H. pylori eradication regimens? (PB AMTCLR)
PPIs standard doses Bismuth subsalicylate Amoxicillin Metronidazole Tetracycline Clarithromycin Levofloxacin Rifabutin
49
What are the current first-line options for H. pylori eradication? (2)
1. PBMT - bismuth quadruple therapy (PPI, bismuth, metronidazole, tetracycline) 2. PAMC - non-bismuth quadruple therapy (PPI, amoxicillin, metronidazole, clarithromycin)
50
What are the second-line options if there is treatment failure or intolerance to first-line H. pylori medication? (2)
1. PAL or PABL - PPI, amoxicillin, levofloxacin - PPI, amoxicillin, bismuth, levofloxacin 2. PBMT if not already attempted
51
What is the last-line option in H. pylori eradication medication?
PAR - PPI, amoxicillin, rifabutin
52
What are the 4 advantages of the PBMT H. pylori regimen?
1. Highly effective 2. Overcomes resistance 3. Preferred if penicillin allergy 4. Similar tolerability to triple therapy
53
What are the 2 disadvantages of the PBMT H. pylori regimen?
1. High pill burden 2. Metro --> alcohol
54
Basically all of the therapies for H. pylori eradication last how long?
14 days
55
How often is each medication in PBMT dosed per day?
P = BID B = QID (BID may be effective too) M = TID-QID T = QID (may be substituted for amoxicillin 1000mg BID)
56
How often is each medication in PAMC dosed per day?
BID for all of them
57
What are the 2 advantages of the PAMC H. pylori regimen?
1. Highly effective 2. Simplified regimen
58
What are the 4 disadvantages of the PAMC H. pylori regimen?
1. More GI ADRs 2. Clarithromycin resistance may impact efficacy 3. Penicillin allergy 4. Metro --> alcohol
59
For H. pylori triple therapy, that is PAC, PMC, and PAM, how often are the medications dosed in each regimen?
BID for all 3 regimens
60
What are the 2 advantages of H. pylori triple therapy?
1. Best compliance 2. PAC available as Hp-PAC
61
What are 4 disadvantages of H. pylori triple therapy?
1. High failure rates 2. Cost if Hp-PAC used 3. Metro --> alcohol 4. Penicillin allergies (except PMC)
62
What is the one advantage of PAL (or PABL)?
Important option for previous failure
63
What are the 2 disadvantages of PAL (or PABL)?
1. Lower eradication rates vs. first-line 2. Penicillin allergy
64
What is the daily dosing of the PAL (or PABL) medications?
P = BID A = BID B = QID L = once daily
65
What is the daily dosing of the PAR medications?
P = BID A = BID R = BID
66
What are the 2 advantages of the PAR medications?
1. Important options for previous failure 2. Low resistance rates
67
What are the 4 disadvantages of the PAR medications?
1. Lower eradication rates vs. first-line 2. Rifabutin expensive 3. Myelotoxicity 4. Use may increase rates of mycobacterium resistance
68
Although it's not used often, explain what sequential therapy for H. pylori is.
PA --> PMC: PPI BID + Amoxicillin 1000mg BID for 5 days followed by --> PPI BID + Clarithromycin 500mg BID + Metronidazole 500mg BID for 5 days
69
What is the advantage of sequential therapy for H. pylori?
May reduce GI ADRs
70
What are the 2 disadvantages of sequential therapy for H. pylori?
1. Complexity 2. High failure rates similar to triple therapy
71
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?
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
What are 2 points that need to be emphasized when counseling someone taking an H. pylori drug regimen?
1. Importance of adherence 2. Expected side effects
73
What are the 2 unique side effects of metronidazole?
1. Metallic taste 2. Alcohol issues
74
What are the 2 unique side effects of tetracycline?
1. Photosensitivity 2. Esophagitis
75
What is the unique side effect of bismuth?
Darkening of tongue/stool
76
What are the 5 unique side effects of levofloxacin?
1. CNS 2. Peripheral neuropathy 3. Photosensitivity 4. Tendon rupture 5. QT prolongation
77
What are the 2 unique side effects of rifabutin?
1. Urine discoloration 2. Myelotoxicity
78
Do we know the local patterns of H. pylori resistance in Saskatchewan?
No
79
What are the Canadian guideline steps of treatment of H. pylori starting with either PAMC or PBMT? (4)
1. Try PAMC or PBMT. If it fails --> 2. Try PAL. If it fails --> 3. Try PBMT. If it fails --> 4. Try PAR
80
What are 3 common reasons for treatment failure of H. pylori?
1. Poor adherence 2. Incorrect regimen used 3. High local resistance
81
There is a debate on whether or not confirmation of H. pylori is routinely necessary, however, it is recommended in what 4 circumstances?
1. Complicated duodenal ulcer 2. Gastric ulcer 3. Gastric cancer 4. Persistent symptoms
82
H. pylori confirmation of eradication should be tested _ weeks after completion of therapy
4
83
H. pylori induced ulcer: Should PPIs be used after H. pylori eradication in duodenal and gastric ulcer? If so, how long?
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
Probiotics in H. pylori-induced ulcer management. Yay or nay? (3)
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
Sucralfate in H. pylori-induced ulcer management. Yay or nay? (3)
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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