PUD and other GI disorders Flashcards
gastrin and acetylcholine signal thru
Gq pathways-calcium induced acid secretion
Somatostain and PG’s signal thru
Gi signalling pathwaays-cAMP pathways- ATP/PKA mediated acid secretion
histamine signals thru
Gs signalling pathways-cAMP/ATP/PKA mediated acid secretion
NSAIDS cause ulcers because
COX2 is protective-loss of PG’s takes away a natural inhibitor of acid secretion-tips the balance in favor of more acid secretion with less ways to counteract it
gastric acid output in gastric ulcers
strangely-normal amount or reduced
gastric acid output for duodenal ulcers
high amounts of gastirc acid output–> esopecially at night
*this is the location of ulcers that dominates in the US
primary factors that cause GERD
increased tRLES's less saliva altered mucosal resistance delayed gastric emptying esophageal dysrythmia?theres a few more but can only remember 4 right now
commonest cause of ulcers
H pylori
virulence factors for H pylori
- flagella
- adhesins
- CagA
- LPS
- UREASE-makes their local environment less acidic–they are trophic for mucosal neck cells within glands
Dx of H pylori
Blood antigen test ( well tell if currently or if ever been infected)
urea breath test-active infection
Ulcer disease DDX
- always consider H. pylori and everyone with it gets treated
- if negative for h pylori-consider NSAIDS
Gastroduodenal ulcer causes
- H pylori
- NSAIDS
- Gastrinoma
- Other
IN the US- H pylori-induced ulcer most likely to show up in
dudodenum-92% of duo-ulcers are due to H pylori
G cells present in
antrum
oxyntic cells present in
body of stomach
IN the US, in people who make a large amount of acid….H pylori usually infects what part of the stomach
the antrum–less acidic environment
if the stomach is making less acid…
H pyloris can infect the corporal (oxyntic) areas-> more likley to cause atrophy in this area
regimine for H pylori infection (not penicillin allergic)
- PPI + clarithromycin + amoxicillin
regimine for H pylori is penicillin allergic
- PPI + clarithromycin + metronidazole
quad regimin for H pylori
> PPI or H2RA + bismuth + metronidazole + tetracyline
*with no subs
if a patient fails initial therapy with clarithromycin involved either from compliance or from lack of efficacy
change the regimen-new one cannot include clarithromycin- the resident strain is considered to be resistant
theory behind antacid
weak bases + strong acids yield salt water and CO2
aluminum and calcium antacids cause
constipation
magnesium compounds cause
diarrhea
antacids effciacy
neutralize acid-short term effect–BUT DO NOT HEAL UNDERLYING CAUSE
antacids and pepsinogen
pepsinogen inactive at pH above 4–normal antacids are effective at inhibting pepsinogen activation
*h2ra’s are not-the inadequately rais pH
dosing for antacids
1 hour and 3 hours after a meal and before bed
do not take antacids with
other drugs-can effect their absroption/efficacy
*take 1-2 hours before other drugs
the only immediate release PPI
IROMC-NAhc03
H1 receptor involed in
urticaria and angiedema
H2 receptor active in
pareital cells in the gut which cause secertion of H
profile for H2RA’s
reduce both volume and H conecntratioon
good at inhibiting BASAL gastric acid secetion-so really only effective at night
*really only good at inhibiting food stimulated acid sec
*do not raise gastirc pH adequateley to inhibit the activation of pepsinogen
*outperformed vastly by PPI’s for PUD and H pylori-worse at mitigating and preventing ulcers
*all OTC with similar effectiveness and varied potency
*less convenient dosing and shorter half lives than PPI’s
SIde effects generally rare and mild–> however, do not (cimetedine-tagamet) take with
theophylline
warfarin
phenytoin
*narrow therapeutic window
the major CYP inhibitor H2AR
cimetidine-tagamet
purifed enantiomers of PPI’s
esomeprazole-all R ismers or omperazole
dexanzoprole? L isomers of one of them i dont rememebr
MOA for PPI’s
*remember-short half lives but the effect are seen long after drug is gone from plasma-thus they are amenaable to once daily dosing
ORAL PRODRUG taken up gradually in the neutral environment INTESTINES (most are entericaly coated and thus absorption is sporadic)–travel in the blood stream-> trophic for parietal cells-> cross the basolateral membrane-are protonated–>travel to apical/lumen border and are sulfated?–> then form a cystein-Sh bond with the H/K ATPase–>permanently inhibit–>cell must code for an entirely new pump
PPI metabolized to a much less extent than others by CYP450
rabeprozole
food and PPI’s
since PPI’s are trophic for pareital cells-> food intake causes Parietal cells to make more acid and icnreases the efficacy of the drug to inhibit the pump
>more acitve the pump is the better it takes up the drug
>this is an added benefit that the H2Ar’s do not have
dosing of PPI’s
once daily-(can be twice but not FDA approved)
-take in morning on empty stomach
>eat 1 hour later
end result of PPI’s
Achlorydia-ALL ALL ALL gastric acid secretion is blocked
inidcations for PPI’s
ZE syndrome-short term
- refractory ulcer
- GERD
- single daily dose safe and effective for over 2 years
how does Bismuth (cytoprotective agent) work?
increases HCO3-secretion
inhibits pepsin (Antacids and PPI’s indirectly inhibit pepsin by preventing it from being activated due to an adequatley elevated gastric pH)
-inhbits h PYLORI?
name the cytoprotective agents
bismuth
sucralfate
Misoprostol-PGE1
Sucralfate MOA
forms sticky, viscous gel that adheres to gastric epithelial cells protecting them from acid and pepsin
only agent in treatment of PUD that requirec an acidic pH for maximal activity
sucralfate
when do you give sucralfate
one hor before bed to promot gastric healing
*remember this is when the stomach is at basal acid levels
used in chronicaly bed ridden patients
example PPI or H2RA induced pneumonia
sucralfate-used acid envirnoment
-ther drugs which induce alkalinization allow bacteria to creeeeeeeeep in
Misoprostol-PGE1 MOA
increases HCO3 production and mucus production
side effect of misoprostol
DIarrhea in 40%-usually intolerable
primarily used in tx of ulcers in pt.’s who MUST use NSAIDS
misoprostol
if clarithromycin and azithromycin resistance is suspected add
furazolindone
postural and dietary management of GERD
decrease gastic size (smaller meal) weight loss bed elevation low fat diet-to increase gastric emptying avoid coffee, mints-these relax LES
H2AR’s only indicated in
mild-infrequent GERD
2 classes to treat gerd
Prokinetics
Antisecretory drugs
prokinetic drugs aim to
improve LES tone and competence
enhance esophageal clearance
hasten gastric emptying
Prokinetics
Metoclopramide-Reglan
Domperidone
Cisapride-not available in US–then why did you fucking put it on here doosher
dopaminergic signalling..
inhibits contraction of gastric smooth muscle
-domperidone and metoclopramide aim to inhibit dopaminergic signalling-thus are prokinetic
Metocloprimide MOA
Dopa (D3R) antagonist-SM agonist
Seritonin (5HT4R) agonist-increases SM contraction-prokinetic
Seritonin (5HT3R) antagonist-inhibits the inhibition-prokinetic
cisapride moa
pure 5HT4R agonist-prokinetic
main side effect of Dromperidone and MAINLY METOCLOPRIMIDE
Tardive Dyskinesia-(from the dopa antagonism)
never give metocloprimide for longer than
1-2 weeks
do all GERD patients make excess acid
*we give them to decrease acid for relief of symptoms and to allow healing
no=only 16%
*h pylori patients make a shit ton of acid though because when the bug infect the cells in the antrum=it causes distrbances and they make a lot of gastrin–gastrin has tropic effects on parietal cells-thus H pylori patients have increased number of parietal cells on average
effects of PPI’s and H2AR on esophageal peristalsin, LES tone, gastric emptying
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