Ulcer Diseases

1
Ulcer Diseases
http//www.gastrointestinalatlas.com/English/Stoma
ch/Gastric_Ulcers_III/gastric_ulcers_iii.html

• April Kooy
• Clayton State University

2
Ulcer Diseases

• Background information
• Statistics
• Pathophysiology
• Types of ulcers
• Factors behind the diease
• Dealing with the disease
• Treatments of Peptic Ulcer Disease
• Close-up of the main types of drugs
• H2-receptor antagonists
• Histamine and its receptors
• Differences between types of medication
• Conclusions
• Future research in ulcers

3
Statistics

• In the U.S., 5 billion dollars spent on drugs
• 2 billion on H2-receptor antagonist a year
• 1 billion on antacids a year
• 3.7 million annually
• 25 million will have peptic ulcer disease.

http//en.wikipedia.org/wiki/Peptic_ulcer
4
Pathophysiology

• Breaks in the mucosa that are exposed to acid
• Found in stomach and duodenum
• Can affect one or all of the stomach layers
• Could extend into the smooth muscles layers

http//harv.rcat.utoronto.ca/cyber_anatomy/HTML/st
omach.html
http//www.daviddarling.info/encyclopedia/S/stomac
h.html
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Diagnosis

• Endoscopy

http//en.wikipedia.org/wiki/Endoscopy
http//www.nursingceu.com/courses/84/index_nceu.ht
ml
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Types of Ulcers

• Stress Ulcers
• Acute form of peptic ulcer
• Accompanies severe illness, systemic trauma or
  neural injury
• 5-10
• Intensive care
• Curling
• Burns, trauma, or hemorrhage.
• Cushing
• Head trauma or brain surgery.

• Peptic Ulcers
• Excess gastric acid production
• 50 occur in stomach
• 70 occur in duodenum
• Pain is aggravated by food and dont happen above
  pH of 2.

• Gastric Ulcers
• Usually normal or reduced levels of acid
• Tends effect older age group. (55-70)
• Pain is aggravated by empty stomach

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Peptic Ulcer Disease

• Environmental factors
• Aspirin and nonsteroidal anti-inflammatory agents
  (NSAID)
• Inhibit COX-1 that is needed for prostaglandin
  synthesis
• Prostaglandins are important in protecting the
  mucosa
• High amounts of Pepsinogen I
• 5X more with high circulating levels
• Chief and mucous neck cells
• Genetic factors
• 3X more in first-degree relatives
• Smoking
• Not alcohol, caffeine or spicy food
• Psychological factors
• A person that operates in a stressful environment

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Peptic Ulcers

• Physiological factors
• Helicobacter pylori
• High percentage of duodenum stomach peptic
  ulcers
• Classified as a carcinogen
• Found worldwide
• When phospholipase A is in high amounts, this
  allows H. Pylori to penetrate gastric mucus.
• Exotoxin Vac A tends to be found in more severe
  cases.
• Diagnosis
• Carbon urea breath test
• Serology for antibodies
• Endoscopy

http//www.bu.edu/bridge/archive/2004/04-02/photon
ics.html
http//www.fondef.cl/fondef/informativo/index_marz
oabril_2005.html
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Zolling-Ellison Syndrome

• Gastrinoma
• G-cells (islet cells) tumor
• Secrete gastrin
• Hormone is important for secretion of acid by the
  stomach
• Slow growing tumor

• Symptoms
• Causes severe acid hypersecretion.
• Leading to peptic ulceration
• High levels of gastrin in the blood

http//adam.about.com/encyclopedia/19253.htm
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Complications

• Hemorrhage
• 20 of cases
• Can be severe, sudden without warning
• Perforation
• Erosion of all layers
• 5 of the cases
• High mortality rate
• Malignant transformation

http//www.umm.edu/imagepages/19235.htm
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Changes for healthy lifestyle

• Alcohol, tobacco, caffeine
• Stimulate gastric acid secretion
• Pepper
• Irritates the gastric mucosa
• Stop taking NSAIDs and Aspirin
• Goal for treatment
• Keep the pH above 5.0
• Reduce the gastric acid secretion
• Reduce the inactivity of pepsin

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Treatments of PUD

• 1 Antacids
• 2 H pump inhibitors
• Binds irreversibly to H/KATPase completely
  blocking acid secretion, until more pumps are
  made.
• 3 Cytoprotective agents
• These increase production of mucus, HCO3- and
  prostaglandins
• 4 H2-receptor antagonists
• Blocks histamine receptors
• 5 Antibiotics
• Eradication of H.pylori

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Antacids

• Weak bases that neutralize acid.
• Compounds
• Aluminum/magnesium hydroxide
• Calcium carbonate
• Magnesium-aluminum trisilcates
• History has shown that antacids have been used to
  treat heartburn and dyspepsia.
• Crushed coral
• Chalk
• Milk
• Alkali

http//subtleenergysolutions.com/newsletter-dicqie
fuller.html
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H pump inhibitors

• Omeprazole (Prilosec)
• Prodrug recommended for long term use.
• Zolling-Ellison syndrome
• It crosses the membrane of parietal cells via the
  bloodstream.
• In a low pH, the drug undergoes a conversion to
  sulfenamide.
• The Active form
• This binds covalently to H/K ATPase.
• Also bacteriostatic

http//www.lek.si/eng/company-overview/about-lek/h
ighlights-2003/
http//c10-ss-1-lb.cnet.com/reference/Omeprazole
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Cytoprotective Agents

• Sucralfate (Carafate)
• Approved in 1981
• About 95 is excreted
• Low solubility and high polarity
• Reacts with HCl
• Binds to positive charged proteins to form a
  protective barrier.
• Activation of mucosal macrophages
• Thought to a source of endogenous prostaglandins

http//c10-ss-1-lb.cnet.com/reference/Misoprostol

• Misoprostol (Cytotec)
• Synthetic prostaglandin analog
• Side effects
• Diarrhea, menstrual spotting, spontaneous
  abortion
• Stimulates secretion of cell proliferation or
  bicarbonate

http//www.luhs.org/HEALTH/kbase/htm/mdx-/drim/153
6/mdx-drim1536.htms
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H2-receptor antagonists
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H2-receptor antagonists

• Little is known of the G-protein linked receptor
• The antagonist block histamine from parietal
  cells
• Parietal cells secrete gastric acid
• Histamine binds to the plasma membrane of
  parietal cells, which eventually causes the
  synthesis of cAMP.
• cAMP activate kinases to produce hydrogen ions.
• All anti-histamines have been associated with CNS
  side effects.
• Can cross the blood-brain barrier
• Headaches, confusion, irritability,
  hallucinations, etc.

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Types of H2 antagonists
http//c10-ss-1-lb.cnet.com/reference/Ranitidine
http//c10-ss-1-lb.cnet.com/reference/Cimetidine

• Cimetidine (Tagament )
• Approved in 1977
• Impairs metabolism of cytochrome P450 drugs.
• 80 Bioavailability

• Ranitidine (Zantac )
• Impairs metabolism of cytochrome P450 drugs.
• 50 Bioavailability

http//c10-ss-1-lb.cnet.com/reference/Famotidine
http//c10-ss-1-lb.cnet.com/reference/Nizatidine

• Nizatidine (Taxac / Axid )
• 72 Bioavailability

• Famotidine (Pepcid )
• 40 Bioavailability

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Antibiotics

• Amoxicillin
• 500 mg
• Three times daily for 14 days
• Usually taken with Omeprazole (Prilosec)
• 20 mg
• Two times daily for 14 days

http//www.drugs.com/pdr/amoxicillin.html
http//ellsworthmaine.com/site/index.php?optionco
m_contenttaskviewid3570Itemid114
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Conclusions

• Future research
• Spend more time getting deeper into the drugs
• Thank you
• Any questions?