Pharm: Acid Peptic Drugs Flashcards
T/F PUD can involve any of the upper GI organs
T
Which cell layer is involved in PUD
PUD includes inflammatory mucosal disorders of the upper GI tract
What kind of receptor is the histamine receptor in the fundus of the stomach?
H2
What kind of receptor is the acetylcholine receptor in the fundus of the stomach?
M3
What activates the H+/K+ ATPase in the parietal cell?
increase in cAMP and intracellular Ca2+
Does the H+/K+ ATPase in the parietal cell use energy?
yes
What other cells support the HCl secretory function of parietal cells?
neighboring enterochromaffin like cells have receptors for ACh and gastrin and secrete histamine when stimulated.
Which excitatory input is not regulated by negative feedback at the level of the parietal cell in gastric acid secretion?
ACh
Which cells secrete pepsin
gastric chief cells
Above what pH is pepsin inactivated?
4
Above what pH is pepsin IRREVERSIBLY inactivated?
6 –> means new enzyme has to be synthesized
T/F pepsin will be inactivated by anything that increases the gastric pH
T
T/F bile can be damaging to the GI lining in the absence of acid.
T
What usually prevents reflux of bile into the stomach and esophagus?
pylorus and LES
Bile gastritis is a consequence of surgery in what kind of patient?
in patients in whom the anatomy of the pylorus has been disrupted (pyloroplasty)
What environmental factor enhances acid secretion and lowers LES pressure?
caffeine
What environmental factor is directly toxic to upper GI organs?
alcohol
What environmental factor may increase acid secretion but does not impair mucosal protective factors?
tobacco
What areas of the GI tract secret bicarbonate?
stomach, duodenal surface epithelia, mucus neck cells, Brunner’s glands
Which prostaglandins enhance cytoprotective mechanisms, increase bicarbonate secretion, increase mucous thickness, and increase mucosal blood flow in the GI tract?
PGE 1 and 2
What structural element in the GI tract ensures mucosal integrity against back diffusion of H+?
tight junctions between gastric cells
What is the target of PPIs?
H+/K+ ATPase
What is the target of H2receptor antagonist?
Rs histamine receptor
How are H2RA’s metabolized?
hepatic p450
How are H2RA’s excreted?
renally
How are H2RA’s dosed?
continuous dosing for a gastric pH of 4
How do H2RA’s work?
blocks H2 to limit H+ secretion –> elevated pH inactivates pepsin
How quickly are H2RA’s absorbed and onset?
rapid absorption and quick onset
What are the primary drug interactions of H2RAs?
- cimetidine binds to p450 and increases levels of warfarin, phenytoin, diazepam
- ranitidine binds less avidly, famotidine and nizatidine do not bind the p450 systme
How do PPI’s work?
irreversibly block H+/K+ ATPase in the final common pathway and reduce acid secretion by parietal cells in lumen
What kind of receptor function do H2RAs have?
competitive antagonist
Of PPIs and H2RAs, which is more effective?
PPIs have more effect and longer lasting effect on acid secretion
How are PPIs delivered?
prodrugs with acid resistant coating
Where is the outer layer of PPIs dissolved?
small intestine –> alkaline environment
T/F lipophilic prodrug of PPI is inactive at neutral/alkaline pH
true
How is PPI prodrug absorbed?
blood stream
What happens to PPIs at the level of the parietal cell?
cross membrane, protonated, concentrated, sulphonated, binds to atpase
Plasma half life of PPIs like omebrazole?
1-2 hours but duration of action is 24-36 hours because of the capsule –> highly effective with single dose inhibiting ~65% of acid secretion
PPI side effects
- high level of gastrin production interferes with negative feedback loop and may cause gastric carcinoid tumors (in rats)
- long term use reduces calcium absorption and reduced osteoclast acid production = hip fx risk
- increased respiratory infections from changed bacteria in GI tract
weak bases that neutralize HCl to form a salt and H2O are called ____
antacids
Antacid adverse effects depend on ____
the specific ion–> but they all have chalky tastes and may affect the absorption of other drugs, specifically tetracyclines
Adverse effects of antacids: Mg
diarrhea, muscle weakness –> Mg accumulation can cause renal failure
Adverse effects of antacids: AL
constipation, binds phosphate (protects against renal failure) –> may contribute to osteomalacia
Adverse effects of antacids: Ca (TUMS)
rebound acid secretion, nephrocalcinosis (“milk alkali syndrome”)
Tx of H pylori
triple/quadruple regimens:
- clarithromycin, amoxiccilin ppi
- clarithomycin, metranidazole, ppi
- levofloxacin, metronidazole, ppi, bisumuth
Misoprostol GI effects
primary prevention of GU in NSAID users, decrease hemorrhage risk if already using NSAID –> use limited by GI side effects of bloating and diarrhea + abortifacient effect
Sucralfate MOA
binds to GI mucosa and stimulates mucous, bicarbonate and PGE2 production/secretion –> increases resistance to pepsin
- not absorbed, no direct effect on acid production
basically coats your tummy and makes you feel better
Misoprostol GI effects
primary prevention of GU in NSAID users, decrease hemorrhage risk if already using NSAID –> use limited by GI side effects of bloating and diarrhea + abortifacient effect
Sucralfate MOA
binds to GI mucosa and stimulates mucous, bicarbonate and PGE2 production/secretion –> increases resistance to pepsin
- not absorbed, no direct effect on acid production
basically coats your tummy and makes you feel better
