GI Ulcer Flashcards
Regulation of gastric acid secretion from parietal cells:
1) Neural stimulation via the vagus nerve secretes _____.
2) Endocrine stimulation via ________ released antral G cells.
3) Paracrine stimulation by local release of _________ from enterochromaffin-like cells.
1) Ach
2) Gastrin
3) histamine
Whats do NSAIDS interfere with in PUD
-interfere with biosynthesis of prostglandins (PGE2 and PGI2) by inhibition of COX-1; luminal presence of the drug plays a minor role.
5 protective factors in PUD.
1) Secretion of a thick mucus layer hat forms barrier against acid and pepsin.
2) Secretion of bicarbonate by superficial epithelial cells.
3) Blood flow maintains mucosal integrity.
4) Prostaglandin secretion stimulated by low pH- attenuates acid production, stimulates secretion of mucus and bicarbonate, promotes vasodilation and inhibits the histamine evoked cAMP-dependent pathway.
5) Rapid turnover of GI epithelia.
4 aggressive factors in PUD.
1) H. pylori
2) NSAIDS
3) Gastric acid
4) Pepsin
If PUD caused by NSAID, what is therapeutic guidelines?
-Stop NSAID or switch to more COX-2 selective agent. Heal with anti ulcer meds.
If PUD from H. pylori, what is the therapeutic guidelines?
Eradication method:
- PPI based 3 drug regimen- PPI, clarithromycin, amoxicillin or metronidazole for 14 days
- Bismuth-based 4 drug regimen- bismuth subsalicylate, metronidazole, tetracycine plus PPI for 10-14 days
What is stage 1 PUD and how would you treat?
<2-3 per week.
-Diet modification, antacids, H2-receptor blocker
What is stage 2 PUD and how would you treat?
> 2-3times/ week with or w/o esophagitis.
-PPI
What is stage III PUD and how would you treat?
Chronic unrelenting heartburn with esophageal complications.
-PPI 1-2x per day.
How do you treat PUD in pregnancy?
-Anacids or sucrafate for most cases; H2 blockers (ranitidine) and PPI (iansoprazole) can be used if symptoms are intractable.
1) What antibiotic is used in PUD and a preferred component due to low resistance/toxicity?
2) What antibiotic has shown increase resistance in PUD?
3) Alternative for patients allergic to penicillins.
4) Used in bismuth-based quadruple therapy.
1) Amoxicillin.
2) Clarithromycin
3) Metronidazole
4) Tetracycline
What is a colloidal suspension in MgAI silicate clay and undergoes rapid dissociation in the stomach?
Bismuth subsalicylate (pepto-bismal)- Salicylate is absorbed whereas bismuth is excreted in feces.
Name the prototype antacid
Magnesium hydroxide-aluminum hydroxide
Name a histamine H2-receptor antagonists and what is the MOA?
Cimetidine- blocks acid secretion from parietal cells that is stimulated by histamine; indirectly decreases gastrin- and ACh-induced acid secretion.
List a proton pump inhibitor and describe the MOA:
Omeprazole- prodrug that irreversibly inhibits H+, K+-ATPase (proton pump)
T/F: Bismuth subsalicylate:
1) Bismuth part has antibacterial activity against H. pylori (cell wall disruption); and can also bind E.coli entero toxins.
2) Forms a barrier that protects ulcers from further damage.
3) Bismuth part has anti-secretory and anti-inflammatory activities.
1) True
2) True
3) False: the salicylate part has this action
Therapeutic uses of bismuth subsalicylate includes:
1) PUD
2) Diarrhea- reduces stool frequency and liquidity in non-specific and acute infection (travelers diarrhea) due to salicylate inhibition of intestinal prostaglandin and chloride secretion.
3) Nausea and cramping…yay Pepto-Bismol
Adverse effects of bismuth subsalicylate includes:
1) Harmless black discoloration of stool and tongue
2) Salicylum- can cause tinnitus
3) Reye’s syndrome
MOA of antacids (mag hydroxide-aluminum hydroxide)
Alkaline compounds that neutralize gastric acid and thus raise stomach pH; potency expressed in acid-neutralizing capacity (ANC) units.
-Most elevate to pH around 5
T/F: Magnesium hydroxide-aluminum hydroxide:
1) Rapid onset with 1-2 hour duration.
2) Al3+ can cause diarrhea (laxative effect) due to stimulation of peristaltic activity.
3) Mg 2+ causes smooth muscle relaxation to counter this effect.
4) Unlike carbonate-based antacids, these ions are not well absorbed systemically(do not increase metabolic acidosis) and do not generate CO2( no belching).
5) Still commonly used for relief of mild symptoms of dyspepsia and GERD.
6) Does not interfere with absorption of other drugs.
1) True
2) False- action of Mg 2+
3) False- action of Al 3+
4) True
5) True
6) False- can interfere- take 2 hr before or after other meds.
T/F: Cimitidine:
1) Competitive inhibitors of H2 receptors on apical membranes of parietal cells; high selective and do not stimulate H1 or H3 receptors.
2) In the presence of H2-receptor blockade, the response to direct stimulation of parietal cells with gastrin and Ach diminished.
3) Increases total acid secretion by about 70% over 24 hours; most effective in increasing basal (and thus nocturnal) acid secretion.
4) Slower onset than antacids but have a longer duration (6-10hrs); can be taken prophylactically.
5) Tolerance can develop rapidly
1) False- basolateral membranes
2) True
3) False- Suppresses instead of increases
4) True
5) True
Cimitidine is therapeutically used for PUD for SHORT/LONG-term therapy. It is used for GERD and best for ___________ use, modest postprandial. Also used in aspiration ___________- anesthesia suppresses the glottal reflex, permitting potentially fatal aspiration of gastric acid to the lungs.
Short term, nocturnal, pneumonitis.
Adverse reactions of cimitidine include:
- Remarkebly well tolerated.
1) Endocrine effects- blocks androgen receptors, causing loss of libido, impotence and gynecomastia.
2) CNS effects
3) Pneumonia
4) Drug interactions- inhibits multiple CYP isoforms
What is this: Activation occurs within parietal cells in the acidic secretary canaliculi; H+-catalyzed formation of a sulfenamide intermediate that is reactive towards Cys-SH groups on the H+, K+-ATPase. Taken 30 min before meals to stimulate acid formation within parietal cells.
Omeprazole- only active pumps are blocked; only 10% of pumps are active in fasting state.
