Flashcards in Peptic Ulcers, GERD Pharm Deck (51):
Categorize gastric acid, HCO3, pepsin and mucus as aggressive vs. defensive factors in the pathophysiology of acid-peptic diseases.
Aggressive factors: gastric acid, pepsin
Defensive factors: mucus, bicarbonate, LES (for GERD)
Name two acid-peptic diseases and describe the gastric injury common to them.
Peptic ulcer disease (PUD)
In all these conditions, caustic effects of aggressive factors overwhelm the defensive factors of the GI mucosa, resulting in mucosal erosions or formation of ulcerations
(Pathophysiology of GERD)
What are the two main patterns of LES dysfunction?
(1) Hypotensive LES (weak sphincter where there's not a lot of tension to keep it chronically contracted)
(2) pathologic transient LES relaxations = more frequent openings
(Pathophysiology of PUD)
What are two major types of ulcers?
What factors promote formation of ulcers?
Gastric and duodenal*
Inc. secretion of gastric acid
Dec. secretion of bicarbonate
*produce more acid particularly @night
What are symptoms associated with GERD?
Atypical: chest pain, hoarseness, chronic cough, sore throat, wheezing
What are symptoms associated with peptic ulcers?
Epigastric discomfort and fullness
What pharmacotherapy is available for treatment of acid-peptic diseases?
(1) agents that reduce intragastric acidity:
H2- histamine antagonists
(2) Agents that promote mucosal defense:
Cytoprotective agents =
Describe the neural, paracrine and endocrine factors that regulate gastric acid secretion
Histamine from ECL cell will stimulate H2 receptor on gastric parietal cell to increase cAMP, resulting in secretion of acid.
Gastrin from blood vessels will stimulate CCK2 receptors on ECL and G cells => release of histamine and increased intracellular calcium, respectively.
Neurotransmitter ACh stimulates M receptors on ECL and G cells to stimulate histamine and increased calcium, respectively
What is the MOA of antacids?
Neutralize gastric acid secreted from G cells (protons released from proton pump)
What is the clinical use of antacids?
Treatment of intermittent heartburn and dyspepsia
What are the instructions for use of antacids?
1 hour after meals
Frequent dosing: q1-2 hrs or to manage acute ulceration
What are examples of antacids? What side effects are expected from carbonate-containing formulations?
carbonate-containing release CO2 = gastric dissension and belching!
What are side effects of sodium bicarbonate antacids?
Fluid absorption - caution in patients with renal insufficiency, heart failure, high BP
Gastric dissension + belching
What are side effects associated with calcium carbonate antacids?
Milk-alkali syndrome: hypercalcemia, renal insufficiency from excessive doses with calcium-containing dairy
Increased gastric acid secretion (since Ca stimulates gastrin)
Gastric distension and belching
What are side effects associated with magnesium hydroxide?
Hypermagnesemia (in patients with kidney disease)
Can chelate drugs in intestine, leading to dec. drug absorption
What are side effects associated with aluminum hydroxide?
Can chelate to drugs in intestine, leading to dec. drug absorption
Absorbed and excited by kidneys - NOT for LONG TERM use in patients with renal insufficiency
Which salts are usually administered together in antacids?
What are examples of H2RAs?
What is the MOA of H2RAs?
Complete with histamine for H2 receptors on the basolateral membrane of parietal cells to inhibit basal acid secretion
What is the clinical use of H2RAs?
Gastric + duodenal ulcers
Zollinger-Ellison syndrome (tumor that autonomically secretes gastrin, leading to increased gastric acid secretion)
How are H2RAs excreted?
Dose reduction in patients with kidney disease
What are adverse effects of H2RAs?
CNS: headache, drowsiness, fatigue, muscular pain
GI: diarrhea, constipation
Tolerance can develop to H+ suppressing effect because eventually enough histamine can be secreted and accumulate to compete with the H2RAs
What are side effects associated with Cimetidine?
Gynecomastia or impotence in men
Galactorrhea (spontaneous flow of milk) in women
What are DDIs with H2RAs?
Compete with creatinine and certain drugs for renal tubular secretion
May alter absorption of drugs with gastric pH dependent bioavailability
Interferes with hepatic pathways - CYP3A4 inhibitor (prolonged halflife of drugs metabolized through these pathways)
What are instructions for use of H2RAs?
Take at bedtime
Reduce nocturnal acid secretion
What are examples of PPIs?
What is the MOA of PPIs?
IRREVERSIBLE inhibitors of gastric H/K ATPase (proton pump) in active parietal cells in stomach
Inhibits both fasting and meal-stimulated secretion
Describe the anatomic route by which PPIs are delivered to the site of action, including the role of acid-resistant coating and acid-mediated activation.
PPIs are prodrugs. They travel through stomach until they are finally un coated by duodenal sphincter and into blood vessel. Activated in the acidic environment of parietal cell, where they bind to the ATPase irreversibly.
What is the therapeutic use for PPIs?
Gastric and duodenal ulcers
Zollinger-Ellison syndrome (tumors that autonomically secrete gastrin)
Briefly explain the difference between esomeprazole and omeprazole regarding its metabolism?
Omeprazole is metabolized by CYP2C19 (racemic mixture)
Esomeprazole is metabolized by CYP2C19 AND CYP3A4 (just the S isomer)
What are adverse effects of PPIs?
N/D, abdominal pain, constipation, flatulence
Modest increase in risk of osteoporosis (since acid helps absorb food-bound minerals like calcium)
Subnormal B12 levels (since acid important for its release from food)
Respiratory + enteric infections (acid = defense barrier!)
Increased serum gastrin => can stimulate hyperplasia of ECL cells and can cause rebound acid hypersecretion w/ discontinuation
What are DDIs associated with PPIs?
Reduced absorption of drugs that require acidic environment, iron
Omeprazole inhibits CYP2C19 = dec. CL of phenytoin, warfarin, diazepam; inhibits conversion of clopidogrel to active form
What are instructions for use for PPIs?
Require systemic absorption before reaching gastric mucosa - so DON"T BREAK enteric coating
Give drug 1 hour BEFORE meal!
What is the MOA of Sucralfate?
Undergoes extensive cross linking in acidic environment (prodrug)
Forms viscous paste that binds selectively to ulcers or erosions
Protection of ulcerated area for up to 6 hours
What is the clinical use of sucralfate?
Peptic ulcers (rarely used though!)
What are adverse effects of sucralfate?
Not absorbed => no systemic AEs
BUT.. aluminum = constipation
What are DDIs associated with Sucralfate?
Antacids = avoid within 30 min.
What are instructions for use of sucralfate?
Take on empty stomach 1 hour before meals
What is the MOA of BSS?
Creates protective layer against acid and pepsin for protection of ulcer site
Stimulates PG, mucus and bicarbonate secretion
Direct antibacterial effects
What is the clinical use of bismuth compounds?
Nonspecific treatment of dyspepsia and acute diarrhea
What are adverse effects associated with BSS?
Black stools + tongue
Reye's syndrome from absorption of ASA
What is an example of a prostaglandin analog?
What is the MOA of misoprostol?
Double protective effect:
1) stimulates EP3 receptors on parietal cells and surface of mucus cells to decrease cAMP, resulting in decreased secretion of acid
2) stimulation of mucin and carbonate
What is the clinical use of Misoprostol?
Prevention of NSAID-induced ulcers
Must be given QID
What are adverse effects associated with misoprostol?
Diarrhea, abdominal cramping
****Contraindicated in pregnancy!!!!!
List the 3 stages of GERD
Stage I: sporadic uncomplicated heartburn, often with known precipitating factor. Often not CC. No additional symptoms.
LESS than 2-3 episodes per week
Stage II: frequent symptoms
Stage III: chronic, unrelenting symptoms; immediate relapse off therapy; esophageal complications
Know the medical management for each stage of GERD.
Antacids and/or H2RA PRN
PPIs more effective than H2RAs
PPI qD or BID
How do you treat PUD caused by H. pylori?
Heal ulcer + get rid of organism:
How do you treat NSAID-associated ulcer?
NSAID is discontinued: H2RA or PPI
NSAID required: PPI daily or BID; H2RA + misoprostol
What is the treatment of a stress-related ulcer?
H2RA or PPI