L4: PUD Flashcards
Defined as a circumscribed loss of the
mucous membrane of the stomach or
duodenum or of any other part of the GI
system exposed to gastric juices
containing acid and pepsin.
PUD
Marked by ulcers or sores located in the
mucus membrane of the stomach (gastric
ulcer) or duodenum (duodenal ulcer)
PUD
ulcers in PUD extends deeper into the…
muscularis mucosa
occur in stomach
gastric ulcers
occur in duodenum
duodenal ulcer
- epigastric pain 1 to 2 hrs after eating
- pain 2 to 5 hrs after eating
- gastric ulcer
- duodenal ulcer
Can cause hematemesis (vomiting of blood)
or melena (blood tarry stool)
gastric ulcer
Can cause melena or hematochezia
(presence of blood in the stool)
duodenal ulcer
Can cause gastric carcinoma (mostly in the
elderly)
gastric
Heartburn, chest discomfort are less
common but may be seen
duodenal
Heartburn, chest discomfort and early
satiety are commonly seen
gastric
Pain may awaken patient during the night
(nocturnal pain)
duodenal
less severe gi bleeding
h pylori induced
rare
condition in which one or more tumors
(gastrinoma) are formed in the
pancreas, which can secrete the
hormone gastrin that stimulates the
production of gastric acid
Zollinger-Ellison syndrome
DISEASES AND MEDICAL CONDITIONS
ASSOCIATED WITH CHRONIC PEPTIC
ULCER
• 2/3 gastric ulcer patients are infected with
H. pylori
• Considered Class 1 Carcinogen (gastric
cancer)
NSAIDS
o Cirrhosis
o Chronic renal failure
o COPD
o Cardiovascular disease
o Organ transplantation
h pylori, enzymes
urease
protease
oxidase
most common cause of PUD
h pylori
PGE2 helps in the secretion of what
mucus and bicarbonates
Superficial mucosal damage consisting of
petechiae (intramucosal hemorrhages)
within minutes of ingestion, and progress to
erosions with continued use.
nsaids
Impairs ulcer healing and may be
associated with ulcer-related GI
complications.
cig smoking
Stress increases cortisol, which stimulates
secretion of …
gastric acid
cause of ulceration
Because of imbalance between
aggressive (acid, pepsin, bile salts)
and protective factors (mucus,
HCO3-)
Secreted from the parietal cells in the body
of the stomach
hcl
duodenal ulcer hcl secretion is increased or decreased
increased
hcl secretion in gastric ulcer increases or decreases
decreased normal secretion
3 receptors in the stomach
neurocrine
endocrine
paracrine
what is released and what is the receptor
neurocrine
Ach
m3 receptors
what is released and what is the receptor
endocrine
gastrin
cholecystokinin B receptor
what is released and what is the receptor
paracrine
histamine
h2 receptor
involved in the inhibition
of the secretion of hydrochloric acid
somatostatin and PGE2
_ & _ will inhibit secretion of
gastrin and hydrochloric acid
Secretion of somatostatin and
cholecystokinin
Exhibits CIRCADIAN RHYTHM
basal stimulated
Accounts for the characteristic nighttime
awakening with peptic ulcer pain
basal stimulated
why is it more effectve to take h2 blockers or ppis at night
Highest gastric acid secretion = night
causes inflammation and
increases development of PUD
CagA- Cytotoxin-associated gene
protein A
induces apoptosis and disruption
of the cellular pathways
VacA- Vacuolating cytotoxin
anorexia is more common at
gastric ulcer (than duodenal ulcer)
COMPLICATIONS OF PUD
- bleeding
- perforation
- Obstruction from edema or scarring
- intractable pain
second most common ulcer-related
complication
perforation
occur with duodenal ulcer
Obstruction from edema or scarring
diagnostic procedure of choice for
suspected peptic ulcer
FIBER-OPTIC UPPER ENDOSCOPY
helps visualize ulceration and assess if
there is bleeding
FIBER-OPTIC UPPER ENDOSCOPY
test for h pylori
- endoscopic test
-nom-endoscopic test
endoscopic tests for h pylori
- histology
- culture
- biopsy urease
- pcr
non endoscopy test for h pylori
UBT
fecal antigen test
serological test
Gold Standard
- >95% sensitivity and specific
histology
Culturing of sample in a media
- Sensitivity testing
- 100% specific
culture
Test of choice at endoscopy
biopsy urease
Generates ammonia to produce color
change
- Rapid results (within 24 hours)
biopsy urease
Tests the genetic material of the
bacteria
pcr
considered a research technique
pcr
the most accurate noninvasive test
(95% sensitivity)
ubt
identifies H. pylori antigen in stool by
enzyme immunoassay using
polyclonal anti H. pylori antibody
fecal antigen test
confirms post treatment eradication of h pylori
fecal antigen test
blood test to detect antibodies againt
H.pylori
serological test
Quantitative; less
sensitive and specific than
endoscopy.
lab based serological test
Qualitative; quick
(within 15 minutes).
office based serological test
NOT used for post-treatment
eradication
serological test
high doses are required for healing: 40 mEq
of base seven times daily
antacids
Now, a non-Rx remedy for heartburn and
dyspepsia.
antacids
FDA requirement if acid neutralizing capacity
should be greater
than or equal to 5 mEq per dose.
rapid onsent antacids
Mg(OH)2, MgO, CaCO3
slow onset antacids
Mg trisilicate and aluminum
compounds
antacids ideal dosing interval
1 and 3 hours after
meals and at bedtime
antacids that should be avoided for px with heartfailure
Heart failure = excess sodium intake
(inc. toxicity) (should avoid systemic
antacids)
antacids to be avoided for px with renal failure
Renal failure = should not use
magnesium or aluminum containing antacids
magnesium and aluminum containing antacids causes what to px with renal failure
mg or al contaminf = hypermagnesemia
nahco3 = systemic alkalosis
Rapidly reacts with HCL to produce CO2
and NACl
sodium bicarbonate
Absorbed systematically and should not be
used for long-term treatment
sodium bicarbonate
sodium bicarbonate produces…
Produces distension and belching (can
cause flatulence and enlargement of
stomach)
ANC of nahco3
1 gram = 12 mEq
Partially absorbed from the gastrointestinal
tract and have some systemic effects
calcium carbonate
Reacts slowly with HCl and can form CO2
and CaCl, causing belching
calcium carbonate
May stimulate gastrin release and thereby
cause rebound acid production
calcium carbonate
CI in calcium carbonate
renal disease
ADR of calcium carbonate
Hypercalcemia, Alkalosis, Renal
failure (milk-alkali syndrome)
Reacts slowly with HCl, forming magnesium
chloride
Mg(OH)2
DOES not produce CO2, therefore does not
cause belching and gastric distention
Mg(OH)2
Not absorbed in the GIT therefore
produces no systemic effects
magnesium hydroxide
antacid that can be used for long term therapy
Mg(OH)2
May produce osmotic diarrhea (common
SE)
Mg(OH)2
Has no systemic effects and no belching,
and causes constipation,
hypophosphatemia and osteomalacia
Al(OH)3
prolonged aluminum use
- phosphate depletion
- reduce calcium absorption: Osteoporosis, Osteomalacia, Neurotoxicity
Used to defoam gastric juice to decrease
the incidence of gastroesophageal reflux
simethicone
h2ra are cleared by a combination of
- hepatic metabolism
- glomerular fitration
- renal tubular secretion
Suppress basal and meal-stimulated acid
secretion
h2ra
most potent at 20mg
famotidine
least potent ; higher dose
needed
cimetidine
used as prophylactic
h2ra
h2ra are taken when
before meals
preferred drug for erosive esophagitis
If with erosive esophagitis, healing is only
at 50%, PPIs are more preferred.
H2 blockers has no effect if?
NSAID-induced
Bioavailability is reduced by antacids
cimetidine
• Decreases the absorption of Ketoconazole
cimetidine
cimetidine adverse effects
• Thrombocytopenia
• Gynecomastia and Impotence
o (androgen receptor antagonist)
• Mental confusion in the elderly
• Low incidence of mild GI upset, headache
5 – 10X more potent than cimetidine
• Does not bind to androgen receptor (no
gynecomastia)
ranitidine
Secreted in milk therefore it should not be
given in lactating mothers
ranitidine
Low incidence of headache and cutaneous
rash
ranitidine
hepatotoxic
ranitidine
Tachyphylaxis compromise its long-term use
famotidine
mild cardiotoxic h2ra
famotidine
is famotidine for long term use?
no
As effective as ranitidine and may be
administered once daily
nizatidine
like ranitidine, this drug may produce hepatotoxicity
nizatidine
doesnt affect cyp
famotidine and jizatidine
One of the most widely prescribed drugs.
ppi
ppis are all?
prodrugs
ppi with the highest bioavailability
esomeprazole amd lansoprazole
fastest onset of action
omeprazole
when should ppis ne taken
Taken 30 to 60 mins before meals (usually
before breakfast)
days after full effect of ppi
3-4days
Undergo rapid first-pass and systemic hepatic
metabolism (needs dose adjustment) and have
negligible renal clearance
ppi
erosive gerd
OD ppi
bid for 3 months for extraesophageal complic of reflux disease
for non erosive gerd
h2ra or ppis prn
heals more than 90% of duodenal ulcers within 4 weeks
ppi
ppi heals more than 90% of gastric ulcers within 6 to 8 weeks
PEPTIC ULCER (NSAID) tx
OD PPI or H2 antagonists + withdraw
NSAID
PEPTIC ULCER (H. PYLORI-ASSOCIATED) tx
Most effective regimen: 2 antibiotics + 1
PPI (triple therapy)
14 day regimen for h pylori pud
1 PPI bid, clarithromycin 500 mg
bid, and 1 g Amoxicillin or 500 mg
Metronidazole bid
o After completion = PPI is still
continued OD 4 – 6 weeks** (for
ulcer healing)**
PREVENTION OF STRESS-RELATED
MUCOSAL BLEEDING tx
Omeprazole orally via NGT
Generally safe but can impair Vit b12 absorption
in long term use
adr of ppi
May cause increased Gastrin levels
(Hypergastrinemia, may return to normal after 1
month of discontinuation)
ppi
inhibits metabolism of warfarin,
diazepam, phenytoin
omeprazole
inhibits metabolism of diazepam
esomeprazole
enhances clearance of
Theophylline
lansoprazole
Given as delayed release capsule because of
acid lability
omeprazole
omeprazole ci
pregnant
Acid labile and administered as an enteric
coated tablet
lansoprazole
• Prodrug that requires protonation for activation
lansoprazole
anticholinergic drugs
Propantheline, Isopropamide and
Scopolamine
Binds to ulcers (up to 6 hrs)
• Protects ulcerated areas from further damage
and promotes healing
sucralfate
stimulates mucosal production of
prostaglandins and inhibits pepsin
sucralfate
sucralfate is taken when
empty stomach 1hr before meals
avoided when using sucralfate
PPIs, H2 antagonists, and antacids
acid is needed for activation
PROSTAGLANDIN E1 ANALOGUE
misoprostol
Has both inhibitory and mucosal protective
properties
misoprostol
misoprostol is given daily __x
3-4x
INCREASES mucus and bicarbonate secretion
by the gastric epithelium by increasing epithelial
regeneration and by enhancing mucosal blood
flow, thus enhancing mucosal protection
misoprostol
binds to a prostaglandin receptor on
parietal cells, reducing histamine-stimulated
cAMP production and causing modest acid
inhibition.
misoprostol
Coats ulcers and erosions, creating a protective
layer against acid and pepsin.
colloidal bismuth compounds
Reduces stool frequency and liquidity in acute
infectious diarrhea
colloidal bismuth compounds
Has direct antimicrobial effects and binds
enterotoxins beneficial for H. pylori infections
bismuth…
should be used for only short
periods and should be avoided in patients with
renal insufficiency.
bismuth agents
Synthetic derivative of glycyrrhizic acid
carbenoxolone
• Heals both gastric and duodenal ulcers
carbenoxolone
AE of carbenxolone
Aldosterone effect (can cause
sodium and water retention, therefore
leading to HTN and hypokalemia)
Impaired pancreatic secretion may cause
steatorrhea (fatty stool), which can lead to fat-
soluble vitamin deficiency (vit ADEK).
octreotide
octreotide adrs
hypothyroidism
bradycardia
acute cholecystitis
Recommended first line option
particularly for those patients who are
allergic to penicillin or clarithromycin.
bismuth salicylate
metro
tera
ppi/h2ra
10 days anti / sequential therapy
1st 5 days
- ppi
- amoxicillin
2nd 5 days
- ppi
- clarithro
- metro/tini
CONCOMITANT THERAPY: HYBRID
THERAPY
1st 7 days
- ppi
- amoxicillin
2nd 7 days
- ppi
- amoxi
- claritho
- metro/tini
