Upper GI Flashcards
Non-pharmacologic therapy for peptic ulcer disease
stop smoking, avoid alcohol and NSAIDs and ASA, avoid irritating foods
General options for pharmacologic therapy for PUD
Eradicate H. pylori, antacids, H2-blockers, PPIs, sucralfate, bismuth subsalicylate, prokinetic agents, misoprostol
Drugs for H. pylori
clartithro + amox or metro + PPI for 14d
or tetra + metro + PPI + bismuth subsalicylate for 14d
or amox + PPI x5d then clarithro + tinidazole x5d
MOA of antacids
quickly neutralize HCl for symptomatic relief of dyspepsia or GERD; does NOT heal erosions
sodium bicarbonate
antacid for PUD; baking soda
ADR: systemic absorption –> Na overload, metabolic alkalosis
calcium carbonate
antacid for PUD
ADR: constipation, acid rebound, hypercalcemia, milk-alkali syndrome (HA, nausea, calcium stones)
aluminum hydroxide
antacid for PUD, very little absorption, used with MgOH to balance GI sx (Mylanta, Maalox)
ADR: constipation, phosphate binding, aluminum absorption
magnesium hydroxide
antacid for PUD, very little absorption, used with AlOH
ADR: diarrhea, Mg accumulation in renal disease
MOA of H2-blockers
dose-dependent inhibition of gastric acid secretion by blocking H2-R on parietal cells; mostly basal/fasting HCl production; slower onset but longer duration than antacids
Uses of H2-blockers
Low doses for heartburn
Higher doses for GERD, PUD
ADR of H2-blockers
generally well-tolerated
high dose -> confusion, delirium, HA, lethargy in elderly
tolerance with repeated use
rebound acid hyper secretion after abrupt discontinuation
pregnancy category B
cimetidine
H2-blocker with shortest duration
ADR: high potential for drug intxn, mod-strong inh of CYP 2C9, 2D6, 3A4
*Avoid in elderly and if on multiple drugs
ranitidine
H2-blocker
intermediate duration, BID
famotidine
H2-blocker
longest duration of action, BID or at bedtime
MOA of PPIs
bind irreversibly to Na/K ATPase in parietal cells, blocking secretion of HCl
*more complete acid suppression than H2-blockers to relieve sx and heal ulcers more quickly
Use of PPIs
GERD and PUD
Metabolism of PPIs
prodrug converted when pH trapped in parietal cells
unstable in gastric acid
delayed onset of action, short T1/2
ADR of PPIs
Short-term: minor HA, constipation, diarrhea, abd pain
Drug intx: inh CYP 2C19 -> dec effect clopidogrel, inc level phenytoin, loss of efficacy of bisphosphonates, reduced abs of itraconazole, PIs
Long-term: inc risk fx, C. diff, CAP, B12-def, hypo-Mg
*Abrupt withdrawal after 3 months = hyper secretion of HCl
omeprazole
PPI
esomeprazole
PPI
also IV
lansoprazole
PPI
also liquid for NG tube
pantoprazole
PPI
also IV; preferred PPI in hospitals
MOA of sucralfate
AlOH complex of sucrose
at low pH binds damaged and ulcerated tissue = physical barrier to prevent injury
*ineffective with H2-blockers or PPI d/t inc pH
ADR of sucralfate
can bind and prevent absorption of drugs like digoxin, quinolone, levothyroxine, phenytoin, warfarin
ADR of bismuth subsalicylate
at pH 3.5, reacts with HCl -> bismuth oxychloride (not abs) and salicylic acid (abs) -> salicylate poisoning like ASA
bismuth sulfate turns tongue and stool black temporarily
MOA bismuth subsalicylate
inhibits pepsin & antimicrobial against H. pylori
GERD pathophysiology
reflux of gastric acid, pepsin, bile acids, pancreatic enzymes into esophagus -> inflammation and complication (directly related to exposure time to acid)
managing GERD non-pharmacologically
weight loss, elevate head of bed, avoid meals 2-3 hours before bedtime
when and how to treat GERD pharmacologically
occasional or non-erosive esophagitis: antacids or H2-blockers
erosive esophagitis: 8 wk of PPI (before 1st meal); switch PPI or increase dose to BID if partial response
receptors in vomiting center of brain
5HT3-R, D2, M
pathway of pharynx -> vomiting
pharynx -> STN -> VC
pathway of blood-borne emetics -> vomiting
BB emetics -> stomach/ small int (5HT3, D2, NK1, opioid-R) -> chemoreceptor trigger zone and nuc/tract solitarius -> VC
pathway of inner ear -> vomiting
inner ear -> cerebellum (M, H1) -> VC
other pathways to cause vomiting
other -> higher centers (NK1, cannabinoid-R) -> VC
What is NK1 receptor
neurokinin-R stimulated by substance P when exposed to chemo, radiation, morphine, nicotine
treating n/v for viral infection, excessive food or EtOH intake, motion sickness
No therapy EtOH
OTC for disagreeable food/overeating: antacids, H2-blockers, Pepto-Bismol (bismuth subsalicylate)
OTC for motion sickness: antihistamines (dimenhydramine), anti-ACh (meclizine)
treating n/v in pregnancy
avoid food with strong odor, eat smaller more frequent meals antihistamine Diclegis (doxylamine + pyridoxine [B6]) up to 3x/d (preg cat A, active ingredient in Unisom for sleep)
treating n/v if mild-mod
monitor hydration
OTC anti-emetic
oral rehydration therapy (as in food poisoning)
types of prescription meds for n/v
D2 antagonists, 5HT3 antagonists, anti-ACh, anxiolytics, synthetic cannabinoids, dexamethasone, subsance P/NK-1-R antagonists
types of D2 antagonists
phenothiazines and metoclopramide
prochlorperazine
phenothiazine D2-blocker
promethazine
phenothiazine D2-blocker
MOA and use of phenothiazines
block D2-R at CTZ level of brain
common for PONV (not as good as 5HT3-blockers)
ADR of phenothiazines
hypotension, sedation, extrapyramidal reactions (acute dystonias)
metoclopramide
blocks D2 at CTZ level in brain
in high doses, blocks 5HT3-R at GI level
ondansetron
5HT3-blocker for n/v
granisetron, dolasetron
5HT3-blocker for n/v
half life 4-8 hours
palonosetron
5HT3-blocker for n/v
IV only; T1/2 40 hours
when specifically to give 5HT3-blockers
before chemo drug exposure
scopolamine
anti-ACh transdermal patch for n/v d/t motion sickness
lorazepam
benzodiazepine; anxiolytic for n/v
used for anticipatory n/v prior to chemo
dronabinol, nabilone
synthetic cannabinoids similar to THC for chemo-induced n/v
ADR: orthostasis, psychomimetic reactions, high abuse potential
dexamethasone
GC for n/v
enhances activity of 5HT3-blockers and metoclopramide
MOA and ADR substance P/NK-1-R antagonists
used in combo with 5HT3-blocker and dexamethasone for highly emetogenic chemotherapy
ADR: metabolized by and mod inh of CYP 3A4
aprepitant, fosaprepitant
substance P/NK-1-R antagonists
treatment of acute esophageal varices bleeding
vitamin K (if elevated INR, common in liver failure), octreotide IV for up to 5d, sclerotherapy
MOA octreotide
somatostatin analogue, potent vasoconstrictor, reduces portal and collateral blood flow
MOA sclerotherapy
inject sclerosing agent like 11.5% NaCl into vein under fiberoptic esophagascope to occlude vein w/i 5 minutes
prophylaxis/ rebleeding prevention for esophageal varices
beta blockers and isosorbide dinitrate
MOA of beta-blockers for esophageal varices
reduces portal vein pressure by decreasing HR (B1 blocked) and splanchnic blood flow (B2 vasodilation blocked)
MOA of isosorbide dinitrate
decrease portal pressure by selective venodilation in splanchnic circulation
