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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)
Where do most ulcers occur?
In the lesser curvature of the stomach and the duodenum
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.
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
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
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
What are NSAIDS?
What is treatment for H. pylori caused PUD?
- 3 Drug Treatment:
- 2 Antibiotics consisting of a combination of Bismuth, Clarithromycin, Amoxicillin, Tetracycline, Metronidazole
- A PPI (Proton Pump Inhibitor)
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
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)
- H2RA's (Histamine-2 Receptor Antagonist)
- Blocks H2 receptors reducing the volume and hydrogen ion concentration.
- Suppresses basal acid secretion and reduces stimulation
- Food decreases absorption
- Crosses blood-brain barrier
What are some adverse effects of Cimetadine?
- Anti-androgenic effects:
- Gynecomastia (Man boobs)
- Reduced libido
- CNS: (Seen with intravenous administration, especially in older patients or with renal or hepatic disease)
- Slurred speech
- CNS depression or excitement
- 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.
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.
Action of PPIs
- 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.
Adverse Effects Omezaprole (PPI)
- Abdominal pain
- Alters metabolic enzymes (P450?)
- Long List of Drug-Drug interactions, so always check to see interactions because it interacts with everything.
What are the 5 most common side effects of drugs?
- abdominal pain
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
What are the actions of Mucosal Protective Drugs
- 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.
- Acute ulcers
- Adverse effects
Other considerations for Sucralfate (carafate)?
- Lots of Drug Interactions
- Not OTC.
- Administered orally only.
What are the actions of Antisecretory Drugs to enhance mucosal defenses
- 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.
What are the adverse effects of Misoprostol (Cytotec)?
- 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.
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