Acid Peptic Drugs Flashcards
(26 cards)
What are the aggressive factors in peptic ulcer disease? (6)
HCL, pepsin, H Pylori, NSAIDs, caffeine/alcohol/tobacco, bile
What are the protective factors in peptic ulcer disease? (5)
Bicarbonate, gastric mucous, postaglandins, mucosal blood flow, mucosal integrity
What are three receptors on parietal cells? Is there cross-reactivity?
H2 receptor
mAChR
Gastrin/CCK-B receptor
No cross-reactivity
Which receptors do ECL cells have? What do they release in turn?
mAChR and gastrin receptors–>secrete histamine when stimulated
What is effect of pepsin on GI tract? How is effect altered?
Pepsin is a protease that can damage GI tract, but it is pH dependent.
It is inactivated at pH>4 and irreversibly inactivated at pH>6
What is mechanism of injury of NSAIDs
Systemic: reduce PGE1 synthesis, anti platelet effect
Direct: Toxic resulting in erosion, reducing protect factors
Who tends to sustain bile related injury to upper GI tract?
Patients who have had surgery where anatomy of pylorus has been disrupted (i.e pylorotomy/pyloroplasty)
What are effects of caffeine, alcohol and tobacco on upper GI?
Caffeine: enhances acid secretion, lowers LES pressure
Alcohol: Directly toxic to UGI
Tobacco: impairs mucosal protective factors
Where is bicarbonate secreted? What is its protective role?
Secreted by stomach, duodenal surface epithelium mucus neck cells, brunner’s glands
Bicarbonate neutralizes HCl
Where is gastric mucous secreted? What is its protective function?
Secreted by stomach/dudoenal epithelium, mucous neck cells, Brunner’s glands
Lubricant/discrete layer that establishes gradient between acidic lumen and neutral cell surface– prevents autodigestion
What are 5 broad approaches to PUD treatment?
- Inhibit acid production
- Acid neutralizers
- Treatment for H Pylori
- Avoidance of NSAID therapy
- Enhance protective mechanisms
How do we inhibit acid production? (2)
H2-receptor antagonist
Proton-pump inhibitors
Describe pharmacokinetics for H2-receptor antagonists: Metabolism, dosing
Rapidly absorbed with quick onset
Hepatic metabolism via p450 and renal excretion
Continuous dosing keeps gastric pH>4, which inactivates pepsin
What are the clinically significant drug interactions of H2 receptor antagonists?
Warfarin, phenytoin theophylline, diazepam
Names of PPIs end in ____
____prazole: omeprazole (prilosec), lansoprazole, rabeprazole
What is the MOA of PPIs? Describe their efficacy
Irreversibly block H/K ATPase– results in more effective and longer lasting reduction of gastric acid production
Describe the activation process of PPIs
Administered as a prodrug that is protonated and sulfonated before it can bind proton pump
What is the effect of the unique properties of PPIs?
Although it’s half life is only 1-2 hours, it has a duration of action of 24-36 hours due to its prodrug requirements
What was the largest theoretical concern of PPI use?
Gastrinomas due to hypergastrinemia secondary to lack of somatostatin…though there is no real evidence in humans of gastrinomas
What are AEs of PPIs
Hip fractures in long-term use due to reduced osteoclast acid production and reduced calcium absorption
What is MOA of antacids?
neutralize acid via sodium bicarbonate (alka seltzer), calcium carbonate (tums) or mylanta
What are adverse effects of antacids?
Toxicity due to taking large doses
Mg: diarrhea/muscle weakness
Al: constipation
Ca: nephrocalcinosis, rebound acid
What are the antimicrobial therapies used for H pylori?
Triple or quadruple regimens: CLAMP
Clarithromycin, levofloxacin, amoxicillin, metronidazole + PPI
What is a natural PGE2 analogue?
Misprostol
