GI I - Acid Peptic Diseases and GERD Flashcards
Key pathogenic agent in peptic ulcers? Functions?
H. Pylori is the key pathogenic agent and it both stimulates acid secretion and destroys stomach protective mechanisms
3 main drug categories to treat peptic ulcers
Druge that:
a. Decrease acid secretion
b. Neutralize stomach acid
c. Promote mucosal defence against acid
3 stomach cells and what do they secrete?
a. Enterochromaffin-like cell: histamine
b. Parietal cell: stomach acid
c. Superficial epithelial cell: cytoprotective mucus and bicarbonate
Histamine antagonists:
- What receptor?
- Functions?
Histamine antagonists:
- H2 receptor
- Blocks histamine but also blocks the potentiated actions of histamine and causes reduces secretion of acid
Prostaglandins:
- What two prostaglandins are important?
- What is their function?
- Agonist?
- Antagonist?
Prostaglandins:
- PGE2 and PGI2
- Protection: stimulate production of mucin and bicarb.
- Misoprostol
- NSAIDS
4 types of drugs with their role in the gastric lumen and role?
a. Proton pump inhibitors
b. Antacids: “soak up” H+ ions
c. H. Pylori medications
d. Cryoprotection: stimulate mucin and HCO3-
Proton Pump Inhibitors:
- These are ___ that require activation in an ___ environment.
- Type of binding? Duration?
- Most ___ suppressors. Reduce by what %?
Proton Pump Inhibitors:
- These are prodrugs that require activation in acid
- Covalent and irreversible binding; long duration of action
- Most potent suppressors. Reduce by 80-95%
Proton Pump Inhibitors:
Drugs?
Proton Pump Inhibitors:
a. Omeprazole
b. Esomeprazole
c. Rabeprazole
d. Lansoprazole
e. Pantoprazole
Proton Pump Inhibitors:
Conversion of drug to a ____ in the acidic secretory canaliculi of the ___ cell. The ___ interacts covalently with ___ groups in the proton pump, thereby ___ inhibiting its activity.
Proton Pump Inhibitors:
Conversion of drug to a sulfenamide in the acidic secretory canaliculi of the parietal cell. The sulfenamide interacts covalently with sulfhydryl groups in the proton pump, thereby irreversibly inhibition its activity.
Proton Pump Inhibitors:
Therapeutic uses?
Proton Pump Inhibitors:
a. Promote healing of ulcers
b. Treat GERD
c. Treat erosive esophagitis
d. Treat pathological hypersecretory conditions (Zollinger-Ellison)
e. Reduce risk of duodenal ulcers with H. pylori infection
Proton Pump Inhibitors:
- Lansoprazole specific FDA approval for?
- Omeprazole is safe and effective for treatment of ____ ___ and ___ in who?
Proton Pump Inhibitors:
- Lansoprazole - treatment and prevention of recurrence of NSAID-associated gastric ulcers
- Omeprazole is safe and effective treatment of erosive esophagitis and GERD in CHILDREN
Proton Pump Inhibitors:
General side effects?
Significant-ish side effect?
Proton Pump Inhibitors:
SE: nausea, abdominal pain, constipation, flatulence, and diarrhea
Significant: Hypergastrinemia - rebound hyperacidity and tumors
Proton Pump Inhibitors:
Drug interactions: what drugs?
Proton Pump Inhibitors:
Interaction with warfarin, diazepam, and cyclosporine
Proton Pump Inhibitors:
What drugs cannot be combined with warfarin?
Proton Pump Inhibitors:
Omeprazole, esomeprazole, rabeprazole, lansoprazole
Proton Pump Inhibitors:
What drugs cannot be combined with diazepam?
Proton Pump Inhibitors:
Omeprazole and esomeprazole
Proton Pump Inhibitors:
What drugs cannot be combined with cyclosporine?
Proton Pump Inhibitors:
Omeprazole and rabeprazole
H2 receptor antagonists:
- Interaction with H2 receptor? What membrane?
- Suppress secretion by ___%.
- Predominantly inhibit? When is this good?
H2 receptor antagonists:
- Reversible competitive inhibition on the basolateral membrane
- Suppress secretion by 70%
- Predominantly inhibit basal acid secretion - good during sleep
H2 receptor antagonists:
Drugs?
H2 receptor antagonists:
a. Cimetidine
b. Rantidine (most common)
c. Famotidine (most common)
d. Nizatidine
H2 receptor antagonists:
Therapeutic uses? (3)
H2 receptor antagonists:
Therapeutic uses:
a. Promote healing of ulcers
b. Treatment of uncomplicated GERD
c. Prevention of stress ulcers
H2 receptor antagonists:
Side effects?
What is common and likely accounts for loss of effectiveness? Occurs after how long?
H2 receptor antagonists:
SE: diarrhea, HA, drowsiness, fatigue, muscle pain, constipation
Tolerance can develop within 3 days and decrease effectiveness
H2 receptor antagonists:
Why has cimetidine declined for clinical use?
H2 receptor antagonists:
Cimetidine inhibits CYPs which decrease its use
Prostaglandin Analogs:
- PGs stimulate?
- PGs decrease?
- PGE2 also stimulates?
Prostaglandin Analogs:
- Stimulate Gi pathway in gastric mucosa
- Decrease intracellular cAMP and H+ secretion
- PGE2 also stimulates mucin pdtn, bicarbonate secretion, and increases mucosal blood flow
Prostaglandin Analogs:
Drug?
Prostaglandin Analogs:
Misoprostol
Prostaglandin Analogs:
Misoprostol:
This is a synthetic analog of ____. It can reduce basal and food stimulated acid secretion by ___%.
Prostaglandin Analogs:
Misoprostol
Synthetic analog of PGE1. Reduce by 75-90%
Prostaglandin Analogs:
- Misoprostol therapeutic use?
- Why is it rarely used?
Prostaglandin Analogs:
- Prevents NSAID-induced mucosal injury and nonsurgical abortion
- Rarely used bc of adverse effects and need for 4 times daily dosing.
Prostaglandin Analogs:
- Adverse effects?
- Contraindications?
Prostaglandin Analogs:
- Diarrhea
- Contraindicated in IBS and pregnant women (promotes uterine contraction)
Coating agents:
In the presence of gastric acid, ___ mediated hydrolysis of ___ proteins contributes to mucosal ___ and ulceration. What can inhibit this process?
Coating agents:
In the presence of gastric acid, pepsin-mediated hydrolysis of mucosal proteins contributes to mucosal erosion and ulceration. This can be inhibited by sulfated polysaccharides
Coating agents:
Drug?
Coating agents:
Sucralfate
Coating agents:
- Sucralfate is a combination of?
- MOA?
Coating agents:
- Combo of octasulfate of sucrose and Al(OH)3
- At low pH it undergoes extensive cross-linking and creates a viscous polymer that sticks to damaged tissue and provides physical protection
Coating agents:
- May also stimulate ___ synthesis and ____ __ ___ locally.
- Use?
Coating agents:
- May also stimulate PG synthesis and epidermal growth factor locally.
- NOT used for peptic acid disease but other conditions in the alimentary tract (such as oral mucositis or proctitis and bile reflux)
Coating agents:
Adverse Effects?
Contraindications?
Coating agents:
SE: constipation
Contraindicated in patients with renal failure (to avoid aluminum overload) and aluminum-containing antacids
Antacids:
Main action?
Antacids:
Function is to relieve symptoms
Antacids:
Speed of reaction of Mg++ hydroxides?
Speed of reaction of Al+++ hydroxides?
Antacids:
Mg++ is rapidly reacting
Al+++ is slowly reacting
Antacids:
What agents are high in Mg++ only?
Antacids:
Mg++ only = Milk of magnesia
Antacids:
What drugs are high in Al+++ only?
Antacids:
Al+++ = Riopan plus double strength and magaldrate
Antacids:
CaCO3 rapidly and effectively neutralizes gastric H+:
However what can its released products cause?
Antacids:
CaCO3:
Releases CO2 = belching, nausea, abdominal distention, and flatulence
Releases Calcium = can induce rebound acid secretion
Antacids:
What drugs are high in CaCO3?
Antacids:
CaCO3 = maalox quick dissolve, calcium rich rolaids, and tums
Antacids:
What causes constipation?
What causes diarrhea?
Antacids:
Constipation = Al+++
Diarrhea = Mg++
Antacids:
What drugs have both Mg++ and Al+++?
Antacids:
Both Mg++ and Al+++
a. gelusil
b. mylanta
Antacids:
What is simethicone and what does it do?
Antacids:
Simethicone is a surfactant that may decrease foaming and esophageal reflux
Antacids:
Drugs high in simethicone?
Antacids:
Drugs high in simethicone:
a. Gelusil
b. mylanta
Antacids:
Adverse effects of Al+++ and Mg++? Thus should not be taken with?
Antacids:
Adverse effects (other than constipation/diarrhea):
May chelate drugs in the GI tract causing the formation of insoluble (thus unabsorbable) complexes.
These should not be taken with other drugs!!!!!
Antacids:
Some antacids contain ___ which is contraindicated! Why?
Antacids:
Some contain aspirin and its contraindicated because it can increase severity or generate ulcers
Bismuth compounts:
Example of drug?
What are they prescribed in combination for?
What do they promote production of in an ulcer?
Bismuth compounts:
Pepto bismol
Prescribed with abx for H. pylori because they are antibacterial
Promote mucin and bicarb production in ulcers
GERD:
What can occur when the LES is damaged?
GERD is a ____ disorder that requires ___ term therapy.
GERD:
Damage: erosive esophagitis, pain, dyspepsia, and barrets esophagus that can lead to esophageal cancer that is INCURABLE
GERD is a chronic disorder that requires long term therapy
GERD:
Stage 1:
Episodes? Other symptoms?
Management?
GERD:
Stage 1:
Less than 2-3 episodes per week. No other symptoms
Lifestyle modification and antacids/H2 antagonists as needed
GERD:
Stage II:
Episodes per week? Other symptoms?
Treatment?
GERD:
Stage II:
Greater than 2-3 episodes per week; w/ or w/o esophagitis
Treat with proton pump inhibitors
GERD:
Stage III:
Episodes? Symptoms?
Managements?
GERD:
Stage III:
Chronic, unrelenting symptoms, immediate relapse off therapy. Esophageal complications
Proton pump inhibitors once or twice a day
