Chapter 27 Upper GI John Noviasky Upper GI Includes

1
Chapter 27 Upper GI

• John Noviasky

2
Upper GI

• Includes dyspepsia
• Peptic ulcer disease
• Zollingers-Ellison, ZE
• GERD
• Stress ulcer prophylaxis

3
Dyspepsia

• Persistent or recurrent pain or discomfort
  (fullness, bloating, nausea) in upper abdomen
• 25-55 will experience
• (fig. 27-1)

4
PUD

• Up to 10 will develop once during lifetime
• 3 main risk factors Helicobacter pylori (H Py),
  NSAID, and smoking
• in those not exposed to NSAID, H Py is common
  cause (90) for PUD
• Fig. 27-2

5
GERD

• Heartburn gt or 2 times per week
• backflow (reflux or regurgitation) of GI contents
  into esophagus
• heartburn - pain in center of chest, burping up
  stomach contents into mouth

6
GERD continued

• If persistent heartburn - more likely to get
  esophageal adenocarcinoma
• Most common cause - inappropriate lower
  esophageal sphincter (LES) relaxation
• some drugs (eg. Verapamil, theophylline)cause
  decreased LES tone

7

• GERD - disease
• Heartburn - symptom
• Esophagitis - endoscopic finding

8
Peptic Ulcer Disease (PUD)

• Lesions in stomach/duodenum as result of
  acid/pepsin
• Zollinger Ellison Syndrome (ZES) - rare,
  hypersecretion d/t gastrin secreting tumor

9
PUD continued

• Incidence of PUD peaked in 50s and has decreased
  since that time - more effective drugs, change in
  hospital coding practice.
• Duodenal ulcers incidence is decreasing
• gastric ulcers about the same may be due to
  NSAID use

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PUD continued

• In Japan - gastric 5-10 times more common than
  duodenal
• in US - duodenal 2 times more common than gastric
• MF for gastric ulcers

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PUD continued

• Gastric ulcers rare before 40 yo, peak 55-65 yo
• Duodenal ulcer incidence increase with age until
  60 yo
• lt 2 have serious complication (bleed,
  perforation, obstruction)

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Physiology of GIT

• Fig. 27-3
• cardia, body and antrum
• Body - 80-90 of stomach
• contains parietal cells - secrete acid and
  intrinsic factor (required for B12 absorption)
• chief cells secrete pepsinogen

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Physiology of GIT cont.

• Antrum
• 10-20 of stomach
• contains G cells - secrete gastrin

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Physiology cont.

• Stimuli trigger secretion of acid
• figure 27-4
• stimulus - cholinergic pathway - parietal cell
  and G cell - release acetylicholine (A)
  eventually gastrin (G) released
• histamine (H) also released
• A,G, H - activates K-H - ATPase in parietal
  cell which secretes H (acid)

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Physiology cont.

• negative feedback - cholecystokinin, glucagon,
  and vasoactive intestinal peptide (VIP) - inhibit
  gastrin secretion

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Physiology cont.

• Protective mechanisms - (protects against pepsin
  and acid)
• prostaglandin E and somatostatin - decrease
  gastric acid secretion and maintain mucosal blood
  flow and stimulate mucus and bicarb.
• Gastric mucus - viscous gel - lubricant, traps
  microorganism, barrier to H

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PUD continued

• Protective Mechanisms (cont.)
• mucosal blood flow -transports O2 to mucosa and
  removes damaging acids
• rapid and continual renewal of gastric epithelial
  cells
• when injured - healing requires formation of
  fibrin cap (aka restitution)
• balance needs to be maintained for healthy GIT

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Pathogenesis

• ZE syndrome - increase parietal cells - increase
  acid secretion
• duodenal ulcers - normal acid secretion
• Gastric ulcers - normal or low acid

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Pathogenesis continued

• Acid in not only mechanism for ulcer production
• decreased mucosal defenses as well (eg. NSAIDs)
  and PG inhibition
• Helicobacter Pylori (H Py) - gram (-) spiral
  bacterium
• found in 90 of duodenal ulcers and 70 of
  gastric ulcers
• not everyone w/H py gets an ulcer
• Increases ammonia which may disrupt gastric mucosa

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Risk Factors (pg. 27-6)

• Disruption of mucosal resistance (eg. H py)
• NSAID use (especially gastric ulcers)
• Cigarette smoking - stimulates gastric ulcer
  secretion and bile salt reflux, alters mucos
  blood flow, and decreases PG production

21
Risk Factors continued

• Foods- caffeine, milk, spicy food - increase H
  and cause dyspepsia BUT no data says they
  increase ulcers
• alcohol - damages mucosa and causes lesions and
  GI bleeding - BUT not proven to cause PUD
• genetics - 20-50 of duodenal ulcers have
  family history
• Stressful life event may cause PUD

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Clinical Presentation

• Pain relieved by food and antacids
• Definitive diagnosis requires endoscopy
• Epigastric pain - may be only symptom not well
  localized annoying, burning, gnawing,
  aching
• Duodenal ulcer pain - episodic, occurs when
  stomach empty (during night, between meals
  relieved by food and antacids)

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Clinical Presentation continued

• Gastric ulcer pain may be similar to duodenal
  ulcer pain but occurs at any time of day.
• However patients with ulcer may not have pain and
  patients with pain may not have ulcer (eg.
  Elderly pt. on analgesic may have ulcer and no
  pain)

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Treatment Goals

• Relief of symptoms (esp. dypepsia)
• Ulcer healing
• Prevention of recurrence
• Eliminate HPy if present
• Decrease acidity
• Increase mucosal defenses
• DRUGS - tables 27-1 and 27-2

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Pharmacokinetics (table 27-3) of H2

• Well absorbed - oral and IV doses similar
• Peak 1-3 hours
• Hepatic metabolism mainly (cimetidine and
  ranitidine)
• Renal elimination mainly - famotidine and
  nizatadine
• All need dose adjustment in renal disease

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Adverse effects of H2

• Most common- diarrhea, constipation, CNS (mental
  confusion, headaches, dizziness)
• Cimetidine-
• anticholinergic effects
• gynecomastia
• impotence
• Hepatoxicity - rare

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Adverse Effects of H2 continued

• Especially at risk - elderly, high doses, renal
  disease

28
Drug Interactions (table 27-4)

• Most prominent with cimetidine -CYP 450
  interaction, reduces clearance of other drugs by
  about 20-30
• most critical with narrow therapeutic rages (eg.
  Phenytoin, warfarin, theophylline)

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Drug interactions continued

• Ramitidine, famotindine and nizatadine have less
  chance for interaction than cimetidine
• decreased absorption of ketoconazole d/t
  increased Ph
• cimetidine, ranitidine and nizatadine increase
  absorption of ethanol by decreasing gastric
  alcohol dehydrogenase

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Dosing

• Night-time dosing similar efficacy to multiple
  daily dosing

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PPI mofA

• Bind to K - H - ATPase (transports acid across
  parietal cell)
• inhibit gastric acid secretion

32
PPI efficacy

• Inhibit gt 90 of gastric acid secretion w/in 24
  hours
• Heals more quickly than H2 antagonists (2-4 wks
  compared to 4-8 wks)
• absolute healing rates similar after usual
  therapy course
• Useful for erosive reflux disease, ZE

33
PPI PK

• PPI are unstable in acid media so they are
  enteric coated
• rapidly absorbed and peak 2-4 hours
• bioavailability 50-80
• eliminated hepatically and plasma T1/2 1-2
  hours, antisecretory effect is 1 1/2 to 3 days

34
PPI PK continued

• PPI dosage adjustment not needed for renal
  dysfunction
• Should be considered with hepatic disease

35
PPI adverse effects

• Infrequent - GI (nausea, diarrhea), CNS
  (dizziness, headache) skin rash, gynecomastia,
  increase liver enzymes.
• In theory - increase gastrin could lead to
  carcinoid tumors - no evidence to support this

36
PPI Drug interaction (DI)

• Omeprazole (increase BDZ, phenytoin, warfarin)
• pantoprazole has fewer DI than omeprazole

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Sucralfate

• M of A - at low ph (2-2.5) binds to damaged and
  ulcerated tissue and forms barrier, no systemic
  effects
• efficacy - similar to H2 antagonists
• dosing QID but 2 gram BID is as effective

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Sucralfate continued

• ADV effects - constipation, dry mouth, nausea,
  rashes
• difficult to swallow
• Drug interactions- many drugs absorption is
  decreased (eg. Digoxin, FQ, ketoconazole,
  levothyroxine)

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Antacids

• Mof A - neutralize gastric acid, provide
  cytoprotective effect (stimulate prostaglandins)
• Efficacy - heals duodenal ulcers in 50-90 of pts
  after 4 wks compared to 25-50 on PCB
• effective with in 5-15 minutes and duration 2
  hours

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Antacids continued

• Dosing - multiple times per day (1 and 3 hours p
  meals and HS)

41
Antacids

• Adverse Effects
• sodium bicarb - systemic alkalosis
• aluminum Hydroxide - constipation, aluminum
  absorption
• avoid in renal insufficiency
• magnesium Hydroxide - diarrhea, Mg absorption,
  avoid in renal insufficiency (lt 20 ml/min)
• Adverse effects -sedation, nausea, vomiting

42
Antacids continued

• Calcium carbonate - high doses (4 to 8g/day) can
  stimulate gastric acid production and cause milk
  - alkali syndrome (hypercalcemic nephropathy with
  alkalosis)

43
Antacids continued

• Drug interactions increased ph - alters
  absorption of ketoconazole digoxin, phenytoin,
  INH (Acid required for absorption)
• Binding cipro and tetracycline absorption
  decreased by gt 50 give cipro 2 hrs before antacid

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H Py eradication

• Most patients with ulcer are colonized with HPy
• Higher ulcer recurrence when HPy positive
• combination therapy preferred (table 27-5)

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Question 2

• What should MB be tested for if PUD is suspected?
• When is endoscopy indicated in pts with PUD?
• Is a positive HPy diagnostic of ulcer?

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Question 3

• Which type of testing for HPy is now commonly
  done because of its simplicity and low cost?

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Question 7

• What is limit of H Py testing by serology?
• In what situations is serology testing most
  useful?
• If JL had tested negative for H Py antibodies,
  what should the clinician have suspected?

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Question 11

• What is the prevalence of endoscopically
  confirmed GI ulcers in NSAIDS users?

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Question 12

• What is the of patients that develop
  symptomatic ulcers after 6 months and 1 year of
  NSAID therapy?
• Why doesnt pain correlate well with associated
  ulcers?

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Question 13

• How do NSAIDs produce gastric damage?
• When aspirin consumption exceeds ____tablets, the
  occurrence of ulcers is increased.
• Does the potential for ulceration still exist
  with enteric coated aspirin?
• Which NSAIDs affect COX-2 to a greater degree
  than COX 1?

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Question 14

• Why should NSAIDs be stopped when treating NSAID
  induced ulcers?
• What variables influence healing rate of NSAID
  associated ulcers?

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Question 14 continued

• What H2 antagonist (and at what dose) has shown
  efficacy to try and prevent occurrence of NSAID
  ulcer?
• Which anti ulcer therapy is recommended if NSAID
  MUST be continued?

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Question 15

• Which NSAID should be considered if NSAID must be
  continued or if pt is at risk for NSAID
  associated ulcers?
• What are risk factors for NSAID associated
  ulcers?
• How does misoprostol work to prevent ulcers in
  NSAID user?

54
Question 15 continued

• What GI symptoms are especially prominent with
  misoprostol?
• How does misoprostol cause diarrhea?
• Why is misoprostol contraindicated in pregnancy?
• How does the effectiveness of PPI compare to
  misoprostol and H2 antagonists?

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Question 15 continued

• What is ZE?
• Note patients with ZE have symptoms similar to
  severe PUD but are more persistant and less
  responsive to standard therapy. May need higher
  dose or even surgery to treat.

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Question 18

• Why shouldnt omeprazole be chewed or crushed?
• Note lansoprazole has solu-tab available for pts
  with difficulty swallowing
• What is GERD
• What is classic symptom of GERD?

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Question 18 continued

• What is atypical GERD?
• What is dysphagia? Odynophagia?
• What is the function of the esophagus?
• What are the 3 pathophysiologic mechanisms which
  predispose a pt to GERD?

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Question 18 continued

• What additional variables can contribute to
  development of esophageal damage?

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Question 19

• What is the characteristic symptom of GERD and
  what is it caused by?
• How can GERD symptoms differ in the elderly?
• What is the frequency of heart burn symptoms (and
  presence of esophagitis correlated with?
• What can aggravate symptoms of GERD?

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Question 20

• What are therapeutic goals of GERD?
• What is Barretts esophagitis?

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Question 21

• What lifestyle changes can decrease reflux?
• Why are antacids primarily adjuncts for GERD
  rather than primary therapy?

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Question 21 continued

• What is the of endoscopic healing seen in pts
  on zantac for 8 wks in grade II vs. grade III
  esophagitis?
• Which is more effective treatment of esophagitis
  6 or 12 weeks of therapy?
• What of pts with esophagitis are healed after 4
  wks of PPI?

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Question 21 continued

• What of pts were healed after 4 wks of
  omeprazole compared to 4 wks of ranitidine?
• Why is sucralfate not widely used to manage GERD?
• What is the effect of metoclopramide on acid
  secretion?
• What is the effect of metoclopramide on
  perisitalsis, gastric emptying, transit time and
  LES resting tone?

64
Question 21 continued

• What are adverse effects of metoclopramide?
• Why is metoclopramide generally not considered
  useful in treatment of GERD?

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Question 23

• What was the remission rate after 12 months of
  omeprazole daily vs. omeprazole TIW vs.
  ranitidine?
• Within how many hours after hospital admission
  can a stress-related mucosal lesion be seen?
• Approximately what of these lesions can bleed
  and how often is the bleed significant?

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Question 23 continued

• What is the occurrence of stress ulcer bleeding
  currently?
• What is the main cause of stress ulcer?
• Are large quantities of acid necessary for stress
  ulcer development?
• Which patients secrete normal or decreased
  amounts of acid?

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Question 23 continued

• Which patients secrete more than normal amounts
  of acid?
• In which patients are mucosal defenses (eg.
  Gastric mucosal flow) often compromised?
• What occurs as result of decreased mucosal blood
  flow?

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Question 24

• What are several risk factors for stress ulcers?

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Question 25

• What is the most important approach to preventing
  stress ulcer and examples of how this is done?
• What is target pH of intragastric contents to
  prevent stress ulcer?

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Question 27

• Table 27-6

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Question 28

• How is bacterial growth affected by increased
  gastric pH?
• Why is this a concern?
• How does sucralfate affect gastric pH?
• Is sucralfate effective at preventing stress
  ulcer?

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Question 28 continued

• Have studies found a connection between
  nosocomial pneumonias and use of H2 antagonists
  (eg. Ranitidine)?
• What can occur in patients on sucralfate who also
  have renal impairment?