Peptic Ulcer disease Flashcards
Symptom complex associated with PUD
Burning epigastric pain exacerbated by fasting and relieved by meals
Types of cyclooxygenases
COX 1: constitutive
COX 2: Inducible
Tissues expressing COX 1
stomach
platelets
kidneys
endothelial cells
basal acid production is highest at
night
prinicipal contributors of basal acid secretion
Cholinergic from vagus
Histaminergic from local gastric sources
Somatostatin is secreted by _______ cells
D
parietal cell receptor for gastrin
gastrin/CCKB
parietal cell receptor for histamine and Ach
histamine- H2
Ach-M3
Why H+ K+ ATPase is inactive in tubulovesicles?
tubulovesicles are impermeable to K+
pH required for pepsin activity
2
pH at which pepsin is irreversibly inactivated and denatured
>=7
Ulcers
breaks in the mucosal surface >5 mm in size, with depth to the submucosa
peak age of incidence of gastric ulcers
6th decade
Why gastric ulcers are less common than duodenal ulcers?
Higher likelihood of GUs being silent and presenting only after a complication develops
Site of duodenal ulcers
first part of duodenum(>95%)
90% located within 3 cm of the pylorus
Size of duodenal ulcers
<1 cm in diameter
ocassionally giant ulcers(3-6cm) are seen
Apperance of duodenal ulcers
margins sharply demarcated
depth at times reaches muscularis propria
Base of duodenal ulcer
zone of eosinophilic necrosis with surrounding fibrosis
Malignant DU
extremely rare
What is the next step on identifying a gastric ulcer?
Biopsy
Site of benign gastric ulcers
distal to junction between antrum and acid secreting mucosa
histology of benign GU
Similar to DU
Benign gastric ulcers are rare in which site?
Fundus
Benign GUs associated with H. pylori are also associated with
antral gastritis
Benign GU not accompanied by chronic active gastritis
NSAID induced
Chemical gastropathy
Foveolar hyperplasia
edema of lamina propria
epithelial regeneration in absence of H.Pylori
extension of smooth muscle fibres into upper portions of mucosa
gastric acid output in Duodenal and gastric ulcers
DU: average basal and nocturnal gastric acid secretion increased
GU:Gastric acid output (basal and stimulated) tends to be normal or decreased
Types of gastric ulcers based on location
Type 1: Body,low gastric acid production
Type 2: antrum,Low to normal gastric acid production
Type 3: within 3cm of pylorus,accompanied by DU,normal or high gastric acid production
Type 4:cardia,low gastric acid production
Characteristic of H.Pylori
gram negative,microaerophilic rod
Transmission of H.pylori
person to person
oral-oral or fecal oral route
Percentage of pts with gastric and duodenal ulcers with H.pylori infection
gastric: 30–60%
duodenal: 50–70%
Diseases caused by H.pylori
Gastritis
MALT lymphoma
PUD
gastric adenocarcinoma
Corpus predominant atrophic gastritis leads to
asymptomatic H.pylori infection
GU
gastric adenocarcinoma
non atrophic pangastritis is associated with
MALT
asymptomatic H.Pylori infection
Why NSAIDs are dangerous?
Over 80% of patients with serious NSAID-related complications did not have preceding dyspepsia
no dose of NSAID is completely safe
Risk factors for NSAID induced disease
advanced age
h/o ulcer
concomitant use of anticoagulants,clopidogrel,glucocorticoids
high dose
multiple NSAIDs
multisystem disease
direct toxicity of NSAIDs to gastric mucosa is due to
ion trapping
Blood group associated with increased risk of PUD
O
Non secretor type
Why O blood group pts may be at high risk for PUD?
H.pylori binds preferentially to O group antigens
chronic diseases with strong association to PUD?
Systemic mastocytosis
alpha 1 antitrypsin deficiency
CKD
CLD
COPD
nephrolithiasis
Chronic disorders with possible association to PUD
hyperparathyroidism
CAD
polycythemia vera
chronic pancreatitis
Infectious causes of non-Hp and non-NSAID Ulcer disease
CMV
Herpes simplex virus
H.heilmannii
Drugs causing Non-Hp and Non-NSAID Ulcer Disease
Bisphosphonates
chemotherapy
glucocorticoids(along with NSAID)
Kcl
MMF
clopidogrel
crack cocaine
Miscellaneous causes of Non-Hp and Non-NSAID Ulcer Disease
Basophilia in myeloproliferative disease
Duodenal obstruction (e.g., annular pancreas)
Infiltrating disease
Ischemia
Radiation therapy
Sarcoidosis
Crohn’s disease
Idiopathic hypersecretory state
______ % of pts with NSAID-induced mucosal disease can present with a complication (bleeding, perforation, and obstruction) without antecedent symptoms
10
Most discriminating symptom of duodenal ulcer
Pain that awakes the patient from sleep (between midnight and 3 A.M.)
two-thirds of DU patients describing this complaint
Typical pain pattern in Duodenal ulcer
Occurs 90 minutes to 3 hours after a meal and is frequently relieved by antacids or food
Fraction of NUD pts presenting with nocturnal pain
1/3rd
Pain in gastric ulcer
discomfort may actually be precipitated by food
Nausea and weight loss are more common in..
DU or GU?
GU
Mechanisms for development of abdominal pain in ulcer patients
acid-induced activation of chemical receptors in the duodenum
enhanced duodenal sensitivity to bile acids and pepsin
altered gastroduodenal motility
Dyspepsia that becomes constant, is no longer relieved by food or antacids, or radiates to the back
indicate a penetrating ulcer (pancreas)
Sudden onset of severe, generalized abdominal pain in PUD
perforation
Jeopardy
indicate a penetrating ulcer (pancreas)
Dyspepsia that becomes constant, is no longer relieved by food or antacids, or radiates to the back
Jeopardy
perforation
Sudden onset of severe, generalized abdominal pain in PUD
Pain worsening with meals, nausea, and vomiting of undigested food
GOO
Most frequent physical exam finding in GU/DU
Epigastric tenderness
Jeopardy
GOO
Pain worsening with meals, nausea, and vomiting of undigested food
Examination finding suggestive of GOO
Succussion splash
Tachycardia and orthostasis in PUD patient
dehydration secondary to vomiting or GI bleeding
PUD pain may be found to right of midline in ________ % of pts
20
Most common complication observed in PUD
GI bleeding
GI bleeding is more common in individuals more than _______ yrs of age
60
second most common ulcer-related complication
perforation
A form of perforation in which the ulcer bed tunnels into an adjacent organ
penetration
Jeopardy
penetration
A form of perforation in which the ulcer bed tunnels into an adjacent organ
Types of penetration in PUD
DU: pancreas
GU: Left hepatic lobe
gastrocolic fistulas
Least common ulcer-related complication
GOO
Types of GOO
Relative: due to peripyloric inflammation and edema
Fixed: mechanical obstruction secondary to scar formation
Rx of fixed mechanical GOO
Surgery
endoscopic dilatation
Symptoms of GOO
New onset of early satiety, nausea, vomiting, increase of postprandial abdominal pain, and weight loss
The most commonly encountered diagnosis among patients seen for upper abdominal discomfort is
NUD
DD for ulcer like symptoms
proximal GI tumors
gastroesophageal reflux
vascular disease
pancreaticobiliary disease (biliary colic, chronic pancreatitis)
gastroduodenal Crohn’s disease
In which individuals empirical therapy for PUD is enough?
<45 yrs of age
Sensitivity of barium meals for detecting DU is decreased in
Small ulcers <0.5cm
presence of previous scarring
postoperative pts
Invasive tests for detecting H.Pylori
Rapid urease
Histology
Culture
Non invasive tests for detecting H.pylori
Serology
Urea breath test
Stool antigen
Disadvantage of serological tests for detection of H.Pylori
Not useful for early followup
Disadvantages of urea breath test
False negatives with recent therapy
Exposure to low-dose radiation with 14C test
Test for H.pylori useful for early followup?
urea breath test
Side effect of aluminium hydroxide
phosphate depletion
constipation
Side effect of magnesium hydroxide
loose stools
Side effects of Mg and Al containing antacids in CKD pts?
Mg: hypermagnesemia
Al: Neurotoxicity
Adverse effect of longterm use of calcium carbonate
Milk alkali syndrome
Milk alkali syndrome
Hypercalcemia
Hyperphosphatemia
renal calcinosis
Renal insufficiency
Side effect of sodium bicarbonate
systemic alkalosis
H2 receptor antagonists
Cimetidine
Famotidine
Ranitidine
nizatidine
Side effects of cimetidine
reversible gynacomastia
impotence
weak antiandrogenic effect
Drug interaction of cimetidine
Inhibits CYT P450
Phenytoin
theophylline
warfarin
Rare adverse effects due to cimetidine
confusion
elevation of transaminases,creatinine,prolactin
Dosing of H2 receptor blockers
Cimetidine 300mg qid
Ranitidine 300mg hs
nizatidine 300mg hs
famotidine 40mg hs
H2 receptor antagonists that donot bind to CYT P450
famotidine
nizatidine
Rare,reversible systemic side effects due to H2 receptor blockers
pancytopenia
MOA of PPI
Covalently bind and irreversibly inhibit H+ K+ ATPase
PPIs admnistered as enteric coated granules in sustained release capsules
omeprazole
lansoprazole
pantoprazole
rabeprazole
pharmacokinetics of omeprazole and lansoprazole
acid labile
dissolves in small intestine at a pH of 6
PPI that can be given in dysphagia pts
Lansoprazole available as a orally disintegerating tablet
Can be taken with or without water
Omeprazole-soda bicarb combination
protect the omeprazole from acid degradation
promote rapid gastric alkalinization and subsequent proton pump activation
PPIs should be administered
Before a meal
Onset of maximum acid inhibitory effect of PPIs
2-6 hours
Duration of action of PPI
72-96 hrs
PPIs inhibit basal and secretagogue-stimulated acid production by >95% after
1 week of therapy
Gastric acid secretion returns to normal levels _______ days after discontinuation of PPIs
2 and 5 days
PPIs and gastrin levels
Mild to moderate hypergastrinemia
No risk for development of carcinoid tumors
Adverse effect of stopping PPI
Rebound gastric acid hypersecretion
worsening of dyspepsia or GERD
Rebound gastric acid hypersecretion
occurs after short duration use(2 months) and lasts for upto 2 months after discontinuation of drug
occurs in H.pylori negative individuals
How to prevent rebound gastric acid hypersecretion?
Taper PPI dose
Add H2 receptor blockers
IF production with PPI use
decreased
but Vit B12 deficiency doesnot develop as stores are adequate
PPIs interfere with absorption of
digoxin
ketoconazole
ampicillin
iron
PPIs that inhibit CYT P450 system
omeprazole
lasoprazole
Adverse effect of longterm administration of PPIs
Community acquired pneumonia
clostridium difficle infection
hip fractures in elderly women
Mechanism of negative effect of PPI on antiplatelet action of clopidogrel
Bind to same cytochrome p450 (CYP2C19)
PPI that has advantage over other PPIs in interaction with clopidogrel
pantoprazole
How to circumvent PPI,clopidogrel drug interaction
give the drugs 12 hrs apart
PPI before breakfast,clopidogrel at bedtime
New PPI with longer half life
Tenatoprazole
Relevance of inhibition of nocturnal acid secretion
GERD
New class of H+ K+ ATPase inhibitors
potassium-competitive acid pump antagonists (P-CABs)
Most common adverse effect of sucralfate
constipation
MOA of sucralfate
Insoluble in water,forms a viscous paste and bind to active sites of ulceration
Physicochemical barrier
binds to trophic factors
enhances prostaglandin synthesis
stimulates mucus and bicarbonate secretion
Sucralfate is avoided in
CRF pts
To prevent aluminium toxicity
Rare adverse effect of sucralfate
gastric bezoar formation
hypophosphatemia
standard dosing of sucralfate
1g qid
Most widely used bismuth containing compounds
CBS(colloidal bismuth subcitrate)
BSS-pepto bismol(bismuth subsalicylate)
adverse effects of bismuth
black stools
constipation
darkening of tongue
neurotoxicity
why the new interest in bismuth containing compounds
anti H.pylori activity
most common toxicity of prostaglandin analogues
diarrhoea
uterine bleeding
uterine contractions
standard dose of misoprostol
200µg qid
__________ % of patients with gastric MALT lymphoma experience complete remission of the tumor in response to H. pylori eradication
50
In whom should H.pylori be eradicated
documented PUD
Duration of therapy for H.Pylori eradication
14 days
Most feared complication with amoxycillin
pseudomembranous colitis
Adverse effects of amoxycillin
antibiotic associated diarrhoea
nausea
vomiting
skin rash
allergic reaction
adverse effects of tetracycline
rashes
hepatotoxicity
anaphylaxis
H.pylori strains are least resistant to which drugs
amoxycillin
tetracycline
Quadruple therapy
Omeprazole (lansoprazole) 20 mg (30 mg) daily
Bismuth subsalicylate 2 tablets qid
Metronidazole 250 mg qid
Tetracycline 500 mg qid
BSS based triple therapy
Bismuth subsalicylate 2 tablets qid
Metronidazole 250 mg qid
Tetracycline 500 mg qid
Bismuth citrate based regimen
Ranitidine bismuth citrate 400 mg bid
Tetracycline 500 mg bid
Clarithromycin or metronidazole 500 mg bid
PPI based triple therapy
Omeprazole (lansoprazole) 20 mg bid (30 mg bid)
Clarithromycin 250 or 500 mg bid
Metronidazole 500 mg bid or
Amoxicillin 1 g bid
Treatment of failure of H. pylori eradication with triple therapy
Quadruple therapy , where clarithromycin is substituted for metronidazole (or vice versa)
pantoprazole, amoxicillin, and rifabutin for 10 days
levofloxacin, amoxicillin, PPI for 10 days
furazolidone, amoxicillin, PPI for 14 days
Next step in pts who have failed two courses of antibiotics against H.pylori
culture and sensitivity
Sequential therapy against H.pylori
5 days of amoxicillin and a PPI, followed by an additional 5 days of PPI plus tinidazole and clarithromycin
recurrent H.pylori infection occuring within the first 6 months after completing therapy
recrudescence as opposed to reinfection
Treatment of NSAID induced ulcer after discontinuation of NSAID
H2 receptor antagonist or PPI
Treatment of NSAID induced ulcer with NSAID continued
PPI
prophylactic therapy for NSAID induced ulcer
Misoprostal
PPI
selective COX 2 inhibitor
NSAIDs with lower likelihood of GI toxicity
diclofenac
aceclofenac
brufen
Any patient who needs treatment longterm with traditional NSAID therapy should be considered for
H. pylori testing and treatment if positive
Test of choice for documenting eradication
UBT
urea breath test
Rx of PU with H.pylori present
triple therapy for 14 days followed by continued acid-suppressing drugs (H2 receptor antagonist or PPIs) for a total of 4–6 weeks
Definition of H.pylori eradication
organisms gone at least 4 weeks after completing antibiotics
preparation before performing UBT
patient must be off antisecretory agents
Why serologic testing is not useful for demonstrating eradication?
titres fall slowly or donot become undetectable
Repeat endoscopy in gastric ulcers
After 8-12 weeks to document healing and biopsy
Refractory ulcer
A GU that fails to heal after 12 weeks and DU after 8 weeks
Stepwise approach to refractory ulcers
- poor compliance,H.pylori resistance
- NSAID use,cigarette smoking
- GU-malignant ulcer
- ZES
Treatment of refractory ulcers
More than 90% of refractory ulcers (either DUs or GUs) heal after 8 weeks of treatment with higher doses of PPI (omeprazole, 40 mg/d; lansoprazole 30–60 mg/d)
Causes of refractory ulcers
Ischemia
crohn
amyloidosis
sarcoidosis
lymphoma
eosinophilic gastroenteritis
Infectious causes of refractory ulcers
CMV
TB
syphilis
