M6 L4 Drugs for Ulcers Flashcards
how are parietal cells stimulated to secrete acid during gastric acid secretion
- gastrin hormone (acts on G/CCK-B-R)
- acetylcholine (acts on M3-R)
- histamine (acts on H2-R)
how is HCL secreted during gastric acid secretion
by H+/K+-ATPase proton pump into the gastric lumen
what is gastrin hormone and how is it secreted during gastric acid secretion
- secreted by G cells in response to: intraluminal dietary peptides, Ach through vagal stim
-passes from blood vessels to submucosal tissue of fundic glands - binds to G/CCK-B-R on parietal cells and ECL cells
what does the vagus nerve stimulate during gastric acid secretion
- stim release of Ach
- binds to M3-R on parietal and ECL cells
what does gastrin and Ach stimulate ECL cells to release during gastric acid secretion
histamine
how is acid secretion turned off
increased [H+] + passing of proteins and fats into duodenum -> stim antral D cells to release somatostatin which further gastrin release which inhibits further gastrin release
ex of acid-peptic diseases
GERD, peptic ulcer, stress-related mucosal injury, zollinger-ellison syndrome
what is the infection that most commonly causes peptic ulcer
helicobacter pylori (>90%)
what is the drug-induced most common causes of peptic ulcer
- NSAIDs
- steroids
- antineoplastics
what is a liquid that is the most common cause of peptic ulcer
alcohol
what are drugs that reduce intragastric acidity when a pt has a peptic ulcer
- antacids
- muscarinic receptor antagonists (anticholinergics)
- histamine-2 receptor antagonists (H2 blockers)
- PPI’s
drugs that promote mucosal defence in pt w peptic ulcer
- sucralfate
- prostaglandin analogs
- bismuth compounds
what are antacids
- widely used OTC drug
- weak bases (alkaline substance): Na, Ca, Al, Mg salts
how do antacids work?
by neutralizing the gastric acid
2HCL (ACID) + Mg(OH)2 (ALKALI) -> MgCl2 (NEUTRAL SALT) + H2O
Systemic Antacids
ex: NaHCO3 & CaCO3
- releases CO2 and gastric distension
- has absorption into the body
- can cause metabolic alkalosis, hypercalcemia, renal insufficiency
- adverse effects: NaHCO3 (fluid retention), CaCO3 (constipation)
- less safe
Non-systemic Antacids
ex: Mg(OH)2 & Al(OH)3
- no effects, no absorption, no release and gastric distension
- adverse effects: Mg salts (diarrhea), Al salts (constipation)
- more safe
- combo of Mg and Al is useful to avoid the side effects!!
what are muscarinic receptor antagonists like in real life
- less effective w more adverse effects
- limited use nowadays
H2 blockers half life, metabolization, and excretion
- half life: 1.1-4 hrs
- metabolized by the liver
- excreted through the kidney
what is the mech of action for H2 blockers
- selectively block H2 receptors on the parietal cells
- decrease gastric acidity (+/- 70%) mainly at night
H2 blocker adverse effects
<3% so pretty safe
- diarrhea, headache, fatigue, myalgias, and constipation
- impotence and gynecomastia - cimetidine
H2 blocker drug interactions
- cimetidine decrease hepatic microsomal enzymes (cytochrome P450s)
- decrease other drug metabolism -> increase drug levels and toxic response
administration of H2 blockers
- oral (twice daily 0.5 h b4 meals)
- IV (limited use)
H2 blocker drug names
…tidine
- cimetidine
- ranitidine
- nizatidine
- famotidine
what are proton pump inhibitors
- most potent acid suppressors
- all contain benzimidazole ring
absorption + half life of PPI’s
- thru intestine
- delayed by food intake
- inactive prodrugs -> activated in the parietal cells
- half life: 0.5-2 hrs
PPIs mech of action
- irreversible decrease H+/K+-ATPase proton pump
- prevents acid secretion into gastric lumen
PPI’s adverse effects
1-5% so pretty safe
- diarrhea, headache, abdominal pain
- low gastric acidity: interfere w vitamin B12 absorption, bacterial colonization
administration of PPI’s
oral
once a day 1 hr b4 meal
PPI availability
Rx, OTC (some)
PPI drug names
…prazole
- omeprazole OTC
- esomeprazole (nexium) OTC
- lansoprazole
- dexlansoprazole
- pantoprazole
sucralfate
- made of sucrose + Al(OH)3
- acts locally in stomach
- reacts w gastric HCL to protect mucosa
- minimal absorption (<3%) -> no systemic adverse effects
- use is limited nowadays
sucralfate administration
- oral
- QID
- 1 hr b4 meals
Misoprostol mech of action
PGE1 analog
- increases mucus secretion and HCO3 -> protects gastric mucosa -> decrease NSAID-induced ulcers
- decreases HCl secretion
misoprostol half life + absorption
short half life: <0.5 hr
- rapidly absorbed and metabolized
administration of misoprostol
- oral - QID
bismuth compounds
2 compounds
- bismuth subsalicylate
- bismuth subcitrate potassium
bismuth compounds frequently used in combination w…
- PPI’s and antibiotics - treatment of helicobacter pylori
- w Kaopectate - treatment of dyspepsia and acute diarrhea
what can bismuth compunds cause
very safe
- can cause harmless black tongue, and black poo
what is helicobacter pylori
- gram -‘ve bacilli
- responsible for >90% of peptic ulcer disease
treatment for helicobacter pylori
- quadruple therapy: PPI + tetracycline + metronidazole + bismuth
- triple therapy: PPI + clarithromycin + amoxicillin (or metronidazole)
10-14 days for eradication of bacteria
what is an ex of a H2 blocker
ranitidine
