GI: Upper GI Tract, PUD, GERD Flashcards
What are the 3 mediators of secretion of acid into the gastric lumen?
- Acetylcholine
- Gastrin
- Histamine
Protein kinase produced by the gastric mediators stimulate what?
The potassium-hydrogen-adenosine (K-H-ATPase) pump on the parietal cell surface (proton pump)
What is the main action of the proton pump?
Pump protons (mainly H) out of the parietal cells into the gastric lumen as HCl (acid)
What are some of the body’s mechanisms of protection of the gastric lining? (5)
Mucus PGE Somatostatin Bicarb Blood flow
Peptic ulcers are breaks in the _______ mucosa and are the result of an imbalance of ____ ________ and ______.
Intestinal
acid production
protection
Peptic ulcers are located where?
Stomach
Duodenum
3 important factors for PUD development:
H. pylori
NSAID use
Cigarettes smoking
Goals of PUD therapy:
Reduce gastric acidity
Enhance mucosal defenses
Eliminate H.pylori
H. pylori is a gram _____ spiral bacterium and is transmitted ______.
Negative
Orally
How does H.pylori cause gastric injury?
Production of a cytotoxin
Breakdown of mucosal defenses
(Presence of H.pylori in the GI tract causes a production of urease which converts urea to form an ammonia ‘cloud’ around the bacteria to neutralize local acid and form a protective barrier. Urease also causes damage to the mucosal cell wall. The body responds to the formation of the alkaline cloud by increasing acid secretion.)
H.pylori must be ______ or PUD will _____.
eradicated
recur
How do NSAIDs induce GI damage?(systemic and topical)
Systemic:
Tips balance of GI protection vs. acid secretion-By inhibition of cyclooxygenase, PGE is decreased, which decreases bicarb and mucus production, decreases blood flow and increases acid secretion. May also damage mucosal by giving off free radicals
Topical: NSAIDs in stomach lumen at a low pH are unionized which allows them to travel to gastric epithelium cells (neutral pH) where they become ionized and trapped= direct cell damage.
GERD is less of an imbalance between gastric acid secretion and protection and more of a disorder in which:
the esophageal mucosa is damaged by reflux of acid into the lower esophagus
Drugs that inhibit acid secretion include:(3)
H2 antagonists
PPIs
Anticholinergic agents
Drugs that neutralize gastric acid: (1)
Antacids
Drugs that protect the gastric mucosa: (3)
Sucralfate
Colloidal bismuth
PGE
Drugs used to eradicate H.pylori:
Antibiotics
How do H2 antagonists work and what are some examples?
Competitive antagonism of H2 receptors to suppress gastric acid secretion
Ex- Ranitidine, Famotidine, Cimetidine, Nizatidine
When do H2 antagonists reach their peak concentration and how are they metabolized and excreted?
1-3hrs
Metabolized: Liver
Excreted: Kidneys
AE of H2 antagonists:
Diarrhea, HA, muscle pain, constipation, fatigue, confusion/hallucination (IV)
What are common DI that can occur with H2 blockers and which one in particular inhibits CYP?
Interfere with drugs that require in acidic medium (ex-atazanavir)
Cimetidine inhibits CYP3A4, 2D6, 1A2
Which drugs cause a total shutdown of acid release because they work late in the acid production cycle and what are some examples?
PPIs Lansoprazole Pantoprazole Esomeprazole Omeprazole Rabeprazole
PPIs are _____ that are converted to _____ drugs in the parietal cell canaliculus.
prodrug
active
MOA of PPIs:
Forms a covalent bond with proton pump. The bond is irreversible, new proton pump must be synthesized to replace
