Peptic Ulcer Disease (PUD) and Inflammatory Bowel diseases (IBS) Flashcards
peptic ulcer disease defined
epigastric pain that is associated with hyperacidity
gastric ulcers
associated with normal or reduced gastric acid output
altered mucosal resistance may be primary factor
duodenal ulcers
associated with high gastric acid output, especially at night
inadequate duodenal bicarbonate secretion, and insufficient acid neutralization are significant contributing factors
etiology PUD
Generally caused by NSAIDs or Helicobacter pylori infection. Therefore, H. Pylori is regarded as the major infectious cause of PUD.
why is H. pylori resistant to harmful effects of the acidic environment?
produce enzyme urease which converts urea in teh stomach juice into ammonia and bicarbonate
goals in treatment of peptic ulcer disease
- eradication of H. pylori
- relief of symptoms
- healing of ulceration
- prevention of recurrence and complications
antacids MOA
- Are weak bases that chemically neutralize acid. By raising acid pH.
- They prevent the transformation of pepsinogen to pepsin. (Goal to raise gastric pH >4).
SE aluminum hydroxides
constipation
SE magnesium hydroxides
diarrhea
Calcium carbonate
gas and acid reflux
therapeutic uses of antacids
- Simple dyspepsia
- Adjuncts to primary therapy with H2 blockers or proton pump inhibitors
simethicone
belch
forms plug to prevent regurgitation
H2 antagonists
famotidine > nizatidine > cimetidine
MOA of H2 antagonists
competitive inhibit (reversible) histamine-mediated acid secretion and also blunt the response to gastrin and Ach
highly selective
H2 histamine receptor antagonists inhibit what
basal membrane, food stimulated nocturnal section
cancer causing agent found in?
Ranitidine was pulled out from circulation because the drug/or a metabolite is associated with increased levels of N-nitrosodimethylamine (NDMA) a cancer causing agent.
Adverse effects and drug interactions of H2 antagonists
infrequent and mild.
may alter the bioavailability of rate of absorption of certain drugs secondary to changes in gastric pH (example aspirin).
cimetidine
Inhibits the activity of cytochrome p450 and thus slows the metabolism of many drugs
Thus if drugs interactions are to be avoided, choose an H2 blocker other than cimetidine
proton pump inhibitors (PPI) MOA
inhibitors of the H ion pump responsible for secreting HCl into the gastric lumen
proton pump inhibitors specificity
- selective distribution of H+/K+/ATPase are in parietal cells
- requirement for acidic pH for drug activation (i.e. they need to be ionized)
- trapping of the drug at its site of action
PPIs are _____ effective than __________ in relieving symptoms of PUD in healing ulcers.
more; H2 blockers
PPIs are _____ effective than __________ in relieving symptoms of GERN and in healing erosive esophagitis.
more; H2 blockers
does tolerance develop with PPIs?
NO, H2
clinical uses of PPI
Zollinger-Ellison syndrome and refractory gastric, esophageal and duodenal
clinical uses of PPI
Zollinger-Ellison syndrome and refractory gastric, esophageal and duodenal
what PPI inhibit acid secretion and effectively orally?
omeprazole and esomeprazole
what PPI is less effective in severe esophagitis?
lansoprazole
what PPI is metabolized to a much lower extent by the cytochrome P450 system?
rabeprazole (aciphex)
what can occur after chronic use of PPIs and H2 blockers?
decreased absorption of vitamin B12 and → deficiency
what are moderate inhibitors of CYP2C19?
omeprazole and esomprazole
what drug is converted to its active metabolite by CYP2C19?
clopidogrel (Plavix) - therefore inhibition of CYP2C19 may interfere with its activation
bismuth subslicylate is also called
pepto bismol
bismuth subslicylate MOA
- enhances secretion of mucus and HCO3-
- inhibits pepsin activity
- chelates with proteins at the base of the ulcer crater and forms a protective barrier against acid and pepsin
- inhibits H. pylori
side effect of bismuth subslicylate
turns the tongue and stool black and can cause tinnitus
sucralfate
forms sticky, viscous gel that adheres to gastric epithelial cells protecting them from acid and pepsin
what drug is the only one it its class to require an acid pH?
sucralfate
given 1 hour before meals and at bedtime to promote gastric healing
what drug is provided to bedridden patients?
sucralfate
misoprostol has what intolerable side effect?
diarrhea
misoprostol is used for what patients?
primarily used for patients who must NSAIDs
also for ABORTION!
clairthromycin MOA
macrolide that inhibits protein synthesis in microbes
amoxicillin MOA
effective against gram negative bacilli
contraindicated in patients allergic to penicillin
tetracycline MOA
second line drug
must stagger its dose when it is given in conjunction with Bismuth
metronidazole MOA
synthetic ABO against obligate anaerobes
furazolidine MOA
nitrofuran antibacterial and antiprotozoal
if resistance to clarithromycin is suspected, replace it with _________
metronidazole
if both clarithromycin and metronidazole resistance is suspected, what drugs is substituted?
furazolidone or rifabutin
what drug is highly active against H. pylori with little resistance?
Rifabutin
metoclopramide MOA
dopamine 2 receptor blocker as well as 5HT4-R agonist, which increases local release of acetyl choline
domperidone MOA
dopamine 2 receptor blocker only
pharm actions of prokinetic
- stimulates GI smooth muscle
- increases amplitude of esophageal contractions
- accelerates gastric emptying
- increases LES pressure
enhance the main anti-reflex mechanism and accelerate gastric emptying
prokinetic side effects
- tardive dyskinesia related to central dopaminergic antagonism
- prescribed for a short time
antisecretory drugs
no effect on LES (lower esophageal pressure), esophageal peristalsis, or gastric emptying
because they work increase gastric pH
