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What is PUD?
- Peptic Ulcer Disease
- A group of upper GI disorders with erosion of gut wall (the GI mucosa doesn’t have sensory pain fibers)
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Where do most ulcers occur?
In the lesser curvature of the stomach and the duodenum
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What is the most common cause of PUD
- H. pylori (bacteria)
- Must evict H. pylori in order to truly treat the disease and not just the symptoms.
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What are the defensive factors in the GI?
- Mucus ~ forms a barrier
- Bicarbonate ~ Helps to decrease acidity
- Blood flow ~ Mucosal integrity
- Prostaglandins ~ Stimulate mucus and bicarbonate; promotes vasodilation; suppresses gastric acid
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What are some aggresive factors in the GI?
- Helicobacter pylori ~ gram- bacteria
- Nonsteroidal anti-inflammatory drugs ~ Gastric and duodenal ulcers
- Gastric acid ~ Zollinger-Ellison Syndrome
- Pepsin ~ Injures unprotected tissues
- Smoking ~ Delays healing ↑ risk of reoccurrence
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What are the conditions that precipitate PUD?
- Develops when harmful effects of acid and pepsin disrupt the normal GI mucosa
- The main precipitating factors are use of NSAIDS (Inhibits the synthesis of prostaglandins) and infection with H. pylori
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What are NSAIDS?
- NON-
- STERIODAL
- ANTI-
- INFLAMMATORY
- DRUGS
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What is treatment for H. pylori caused PUD?
- 3 Drug Treatment:
- 2 Antibiotics consisting of a combination of Bismuth, Clarithromycin, Amoxicillin, Tetracycline, Metronidazole
- Plus
- A PPI (Proton Pump Inhibitor)
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What is SRMD?
- Stress Related Mucosal Disease
- “Stress Ulcers” related to conditions of physiological stress especially in the critically ill.
- Splanchnic hypoperfusion is most likely caused by gastric mucosal ischemia: Profuse poorly-->decreased mucous production--> increased risk of ulcer.
- Stress leads to increased catecholamine release --> vasoconstriction and decreased cardiac output which decreases GI blood flow
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What is Barret's Esophagus?
- Premalignant condition where the cells that normally line the esophagus are replaced with specialized columnar cells which are not mucus producing and wear out quickly.
- Esophageal adneocarcinoma occurs in about 10%
- At Risk Are:
- White men (Average age of diagnosis – 55)
- History of Gastro-esophageal Reflux Disease (GERD)
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Cimetadine (Tagament)
- H2RA's (Histamine-2 Receptor Antagonist)
- Action:
- Blocks H2 receptors reducing the volume and hydrogen ion concentration.
- Suppresses basal acid secretion and reduces stimulation
- Pharmkin:
- Food decreases absorption
- Crosses blood-brain barrier
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What are some adverse effects of Cimetadine?
- Anti-androgenic effects:
- Gynecomastia (Man boobs)
- Reduced libido
- Impotence
- CNS: (Seen with intravenous administration, especially in older patients or with renal or hepatic disease)
- Confusion
- Hallucinations
- Slurred speech
- CNS depression or excitement
- Others:
- Hypotension if administered by IV bolus (typically is given this way.)
- Candida caused by increased stomach pH, also in other mucosal systems.--> yeast nfxn in women, especially if also on PPIs.
- Thrombocytopenia – D/C if platelets fall below 50,000 (always check platelet levels if pt is known to be taking Cimetadine.)
- Nosocomial pneumonia: Stomach pH is not destroying agents of nfxn.
- Interferes with cytochrome P450--> increase chance of toxicity because other drugs are going to have increased activity.
- Will interact with antacids: take 1 hr before or 2 hrs after taking the antacid to minimize effects.
- Tolerence will develope if used >14 days.
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Proton Pump Inhibitors
- Omeprazole (Prilosec)
- The Proton Pump is the gastric H+/K+ - ATPase enzyme system found in the parietal cells of the stomach. This pump moves hydrochloric acid into the stomach to maintain an acid environment.
- PPI’s irreversibly bind with the proton pump blocking the final stage of hydrogen ion secretion so little or no acid (H+)moves into the stomach
- Acid production is completely shut down, meaning is more efficacious than H2 receptors.
- H2 receptors will still be active, but vast majority of H+ will be blocked.
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Action of PPIs
Omeprazole (Prilosec)
- Generally considered drugs of choice to treat PUD, GERD and SRMD
- Omeprazole (Prilosec)
- General low incidence of adverse effects and is well tolerated
- Therapeutic goal is a gastric pH above 4
- (Normal stomach pH 1.5-3.5)
- It is a PRODRUG and is converted inside the parietal cells (Cells of the stomach lining.)
- Drug of choice because has fewer side effects than H2 receptor blocker.
- Prodrug: Is activated in liver (after metabolism)
- Parietal cells: Cells of the stomach lining.
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Adverse Effects Omezaprole (PPI)
- HA
- Nausea
- Abdominal pain
- Diarrhea
- Alters metabolic enzymes (P450?)
- Long List of Drug-Drug interactions, so always check to see interactions because it interacts with everything.
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What are the 5 most common side effects of drugs?
- Nausea
- vomiting
- diarrhea
- abdominal pain
- constipation.
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What are some considerations when administering Omeprazole? (PPIs)
- Take medication on an empty stomach 30-60 minutes before meals
- Increased risk of hip fracture and osteoporosis with long term use (>6 months), so...
- ...not good idea to administer to elderly, post-menopausal women, frail-boned, Hx of fractures, pts with insufficient calcium intake especially as a teen.
- The drug is acid labile (likely to chemically change in acid).
- It is an enteric coated granule, so DON’T CRUSH
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What are the actions of Mucosal Protective Drugs
Sucralfate (Carafate)
- Action:
- Protective barrier up to 6 hours
- Requires an acid pH, so don’t administer with H2RA or PPI or Antacids
- Prevents bacteria/acid from interacting with stomach, so limits amount of absorption that will happen in stomach.
- Uses:
- Acute ulcers
- Adverse effects
- Constipation
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Other considerations for Sucralfate (carafate)?
- Lots of Drug Interactions
- Not OTC.
- Administered orally only.
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What are the actions of Antisecretory Drugs to enhance mucosal defenses
Misoprostol (Cytotec)
- Prostoglandin analog—promotes ulcer healing by stimulating mucus and bicarbonate secretion and modestly inhibiting acid secretion
- Used for NSAID longterm prophalaxsis to help prevent PUD.
- Was first used to protect urinary tract for people with UTI.
- Symbiotic: work better together than apart.
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What are the adverse effects of Misoprostol (Cytotec)?
- Diarrhea
- Abdominal pain
- Dysmenorrhia (painful mencies) and spotting
- Contraindicated for pregant women: Must be sure (ie pregnancy test, pt currently menstruating) that pt is not pregnant before administering Rx.
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General actions and info on antacids...
- Neutralize stomach acid. Does not decrease production and actually up regulates production of H+.
- Decreases destruction of gut wall
- May stimulate production of prostaglandins
- Adverse reactions:
- Aluminum products (Mylanta)~Constipation
- Magnesium products~Diarrhea
- Calcium Carbonate (Tums, Rollaids)~Constipation; acid rebound
- Sodium bicarbonate~Just Shouldn’t use
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