GERD & PUD Flashcards
normal physiology of the EG and LES for the function of GERD and PUD
what happens when GERD occurs
EG: esophagogastric junction
- esopohagus to stomach: the EG junction is maintained by the LES: lower esophageal sphincter
- when the sphincter is contracted: prevents the backflow of gastric substances into the esophagus
LES: a muscular ring innervated by the vagus nerve that contracts and relaxes
- normally exists in a contracted and closed off state to avoid backflow
In GERD…
- there is an excessive backflow of gastric reflux ino the esophagus
- this leads to a breakdown in the mechanisms of defense within the esophagus (the acid of the stomach is too potent)
- this irriates the esophagus and leads to GERD symtpoms
other causes of GERD
- foods
- meds
- conditions
Conditions
- hiatal hernias: causes LES displacement by protruding through the diaphragm; gastric contents gets stuck & causes symptoms
- esophageal clearance: the time that the acid is mixed with the mucosa
- mucosal resistnace: breakdown of the barrier
- composition of refluxate: the pH of the acidic reflux
- gastric emptying: improper emptying leads to build up and backflow
Food
- mint
- chocolate
- fatty foods
- coffee
- carbonated beverages
- teat
- chili peppers
- garlic
- onions
Meds
- anticholenergics
- barbituates
- caffeine
- CCB
- estrogen
- alcohol
- narcotics
- nicotine
- progesterone
- theophyilline
Direct Irritants
- bisphosphanates: for osteoperosis
- chemo
- iron supps.
- NSAIDS
- KCl
- spicy foods
- organge juice nad tomato jucie
- coffee
Obestiy
Pregnancy
Stress
Tight Clothing
all have the abiity to worsen gerd symptoms
complications of GERD
why do we treat
- we treat to aleviate pt. symptoms and QOL improvement
- significant morbidity if left untreated (risk of barretts)
Complications
- Barretts
- aspiration
- perforation
- hemorrhage
- strictures
- adenocarcinoma
Non-Pharm Management of GERD
Dietary Changes
- decrease fat consuption
- increa protein
- avoid spice & citrus
- alcohol avoidance
- eat in smaller, frequent meals
- avoid eating within 3 hours of sleeping
Lifestyle Changes
- elevated HOB 6-8 inches when sleeping
- weight loss
- stop smoking
- avoid tight fitting clothing
- wait 2-3 hours to lay down after eating
what are the four classes of GERD meds
- antiacids
- Histamine 2 receptor antagonists
- PPIs
- prokinetic agents
what is the physiology of gastic acid secretion
gastric acid (H+) is secreted by teh parietal cells through the proton pump (H+/K+/ATPase pump)
this pump creates a pH of the gastric lumen to be about pH= 3 (because its pumping so much H+ in
- transfers the H+ in the parietal cells in exhcnage for a K+
the parietal cells have 3 different receptors: which when activated will increase the ability of the proton pump in the parietal cell to release H+ (gastric acid)
1. acetylcholine (M3)
2. Gastrin (CCK-B)
3. histamine (H2)
Antacids
- MOA
- when are they used
- drug interactions
MOA: work as weak bases –> they do not act directly on the proton pump but instead reduce acidity within the stomach by neutralzing the gastric acid and pepsin
when they are used
- used as needed: PRN
- quick onset of action
- short-term use: not indicated for chronic use
Drug interactions
- chelation: can bind and prevent absorbtion of other drugs in the stomach as they are just weak bases!
Antacids
- drugs and their side effects
watch all these meds in those with renal failure due to the inabiiltiy to excrete electroyltes and thuse build ups may occurr
Mg(OH2) = milk of magnesia
- side effect = diarrhea, watch in renal failure
CaCO3 = tums, maalox
- side effect = constipation
AI(OH3) = alternaGEL
- side effect = constipation
NaHCO3 = alka-seltzer
- side effect = milk-alkal syndrome (high calcium leads to alkaline)
combination meds
- CaCO3/Mg(OH2)
- AI(OH3)/Mg(OH2)
Histamine Receptor antagonists (H2RAS)
- MOA
- drug interaction
- drug names
MOA: work to competitively, reversibly bind to inhibite the histamine frm binding to the H2 receptor therefore stopping gastric acid (or reducing) its secretion
Drug Interaction
- Cimetidine: interacts at CYP therefore is the last choice of the drug class
Drug Names
- cimetidine
- famotidine (MC used)
- Nizatidine
PPIs
-MOA
Drug Interactions
MOA: work to covalently bind to the H+/K+/ATPase (proton pump) of the parietal cells -> work in a dose-response measure to inhibit the gastric acid secretion
- PPIs are prodrugs meaning thye MUST be exposed to the acidic environment in order to work properly
- theyre more effective because they bind directly ot the proton pump on the parietal cell, not like the H2RAs which bind to histamine
Drug Interactions
- clopidogrel: said that PPIs can decrease their effectiveness but for those with GERD symptoms PPIs are still indicated for use because benefit > risk
- drugs which are pH dependent: they wont work as the PPI will decrease acidity in the stomach
PPI Drug Names
end in -azole
- omeprazole
- esomeprazole
- lansoprazole
- dexlansoprazole
- pantoprazole
- rabeprazole
compare the timing, onset of action between…
- antacid
- H2RA
- PPIs
antacids: QUICK ( < 5 mins) onset, last 20-30 mines
H2RAs: best for anticipation of symptoms onset 30-45mins, lasts 4-10 hours
PPI: takes 2-3 hours last 12-24 hours (best best symptomatic relief)
Monitoring and Pt. Education
- H2RAs
- PPIs (long term use risks?)
H2RAs
- generall well tolerated
- HA, fatigue, dizzy, diarrhea constipation
- renallly dose adjusted
PPIs
- generally well tolerated
- HA, nausea, dirrhead, constiation
- long tearm use: possible osteoperosis, c. diff, CAP, vit b12, hypomag. = why you assess their need to continue med long term or not
Pt. Education
H2RAs
- take with or without food
- symptoms better in a few hours
PPIs
- take ONCE a day 15-30 minutes before you first meal : the PPI can only bind to the pumps which are ACTIVELy secreting the gastric acid
- do not chew/crush
- can pout contents of the pill intp apple sauce for those who cannoy swallow pills
- can take days to see full effect
how to appraoch treatemnt of GERD
- symptoms are frequent (without alarm) = what treatment
- who will relapse after d/c or treatment
- how do you manage specifi symptoms
GERD symptoms frequently
- start an 8 week one before meals PPI trial
- if they have resolution of symptoms = stop the PPI
- if the symptoms return after stopping, restart
- if symptoms are not resolved after 8 weeks = upper EGD - see barretts or not
Maintenance Thearpy
- large amoutn of people will relapse after d/c the PPI
- H2RA: can be used if mild symptoms; watch rebound decreased efficacy (tachyphylaxis)
- PPIs: DRUG OF CHOICE for moderate to severe esopagitis, and barretts (administer at lowest possible dose)
questions to ask to ensure pt. is adhearing to PPI treatment
note on twice daily dosing
- verify adhearance
- verifty their taking it 30-60 mins prior to first meal of teh day
- twice daily dosing: can be helpful, limited data
- GERD not PPI refractory until there is a trial of the twice daily treatment
specifics of PPI Long Term thearpy
pts. with non-erosive reflux disease aka nonerosive GERD can use on-demand PPI or intermittent PPI for a few days/weeks when they have flairs of symptoms
must watch the adverse drug reactsion (vit b12, osteoporosis, calcium, mg issues) thus, de-escalation of this thearpy is essential
alternative option
- the use of H2RAs is acceptbale in those with nonerosive GERD –> but watch the rebound symptoms with the H2RAs
Promotility Agents for GERD
- Metoclopramide
- MOA
- when is it used
- adverse effects
MOA: a dopamine antagonist: activating dopamine will inhibit cholinergic smooth muscle stimualtion, therefore blocking this will allow for gastric emptying and intestinal transit , increasing the tone of the LES
When is is used
- 4x daily medication
- no real role or place in management of GERD due to teh severe side effects unless there is signs of gastroparesis, then this is helpful
SIde Effects
- movement disorders, restlessness
- tachphylaxis: less effective with increased used
Pathophysiology of PUD
- what is chronic peptic ucler diseae
PUD = peptic ulcer disease
- erosions within the lining of the GI tract (primariliy the stomach and the duodenum) that penitrates the muscularis mucosa
- these lesions/ulcers exisit in sizes > 5mm
Chronic Peptic Ulcer Disease
- a frequent recurrance of the ulcers – needing medications to help with the prequent exacerbations
- characteized by exacerbations and remission periods repeatedly
in sum, the patho behind PUD is a imbalance between acid secretion and the protective factors of the GI tract = causing ulcerations
what are the most common reasons for the development of PUD?
what about the uncommon causes?
most common
- H. Pylori infection
- NSAID use
- severe physiologic stress = SRMD: stress related mucosal damage (such as sepsis, ICU, etc.)
less common
- Hypersecretion of gastric acid (Zollinger-Ellison Syndrome)
- viral infections (CMV)
- Crohn’s Disease
- idiopathic
patient risk factors which make them more succeptible to developing PUD
- smoking
- alcohol usage
- age (older)
- stress & diet have been associated with an increased risk = dyspepsia or PUD independet risk (shown to increase the symptoms of the ulcer, not so much as increasing the risk of developing one)
which cells are involved in the acidic and protective factors in the GI tract (2)
- how are they activated and what do they do
how do specific factors (alcohol, smoking) directly impact the defense mechanisms of the GI tract
Chief cells: pepsinogen precursor cells which when there is an acidic environment, this prompts them to create pepsin which helps breakdown proteins (proteolytic)
- overactiviation of these cells in the presence of increased acid aids in ulcer formation
parietal cells: secrete gastric acid via acitivation by histamine (H3), CCK-B which actiavte the proton pump to increase the acidity within the GI
- overactiavtion of these increase the acidity and desrupts the intergrity of the mucosal lining
H. Pylori & Reflux of bile = directly breakdown the mucosal defense and bicarb layer
excess pepsin & gastric acid = breakdown the bicarb protection
NSAIDS = breakdown the prostoglandins and epithelial resistance
alcohol = inihibt epithelial cell renewal
smoking = inhibits vasculature flow
Etiology of an H. pylori infection & resulting PUD
H. Pylori
- a gram negative spiral, flagellated bacteria which is pH sensitive
- the flagella and their spiral shape help them move to the mucus layer (where its pH neutral)
- the h. pylori have urease: which hydrolyze urea in the gastric acid and convert it to ammonia and CO2: ammonia then can neutralzie the gastric acid
- the h. pylori also produce acid inhibitory proteins which allow them to exisit in the acidi environment
how H. pylori causes PUD
- the h. pylori produce a toxin - which directly damages the host’s immune reponse
- this creates chronic gastritis (increased inflammatory response)
leadsing to…
- PUD
- gastric cancer
- MALT lymphoma
General Approach of H. Pylori Treatment
every regimen includes
- PPI (or other anti-secretory agent)
- 2 anitbiotics
Triple Thearpy
- 2 anx. + PPI
Bismuth Therapy : Quad
- bismuth
- 2 abx.
- PPI
example: bismuth + PPI + metronidazole + tetracycline
non-Bismuth Thearpy:
- amoxicillin
- metronidazole
- clairthromycin
- PPI
treatment for 10-14 days
dosing with a PPI for PUD is 2x daily while fro GERD its only 1x daily
Clairythromicin: need to assess for macrolide exposure & resistance if >15% you need to use something else
Amoxicillin: watch if PCN allergy
Monitoring for Efficacy and Toxicity in H Pylori treatment
Efficacy
- treat for 10-14 days
- continue acid suppresion treatmetn via PPI for 2 weeks or 4 weeks with H2RA (PPI preferred)
DO NOT test for resolution of h. pylori if the symptoms have resolved, no need
Adverse Drug Reactions
Clairthromycin: nausea, diarrhea, abnormal taste
Amoxicillin: nasuea, vomitting, dirrhea
metronidazole: nausea, vomiting, metallic taste
tetracycline: nasuea, vomiting
Education for Pt.
- antibiotics: finish full course of them!
Metronidazole: avoid alcohol
Tetracylcine: take on empty stomach, not with antacids and can make photosensitive
Treatment Failure of H. pylori related PUD
treatment aimed at using antibiotics whichwere not previiously used or associated with resistance
- if first line treatment included clarithromycin…
- use bismuth quad
- use levofloxicin
- rifabutin triple - if first line was bismuth quadruple…
- levofloxicin
- concomitant
- rifibutin triple
can test for succeptibility
Etiology of NSAID releated PUD
NSAIDS
- systemic inhibition of prostoglandins; which normally have a cytoprotective effect
- additionally, have a direct irritation property of the gastric epithelium due to the acidic property of NSAIDS
NSAIDS: act on the COX1 and COX2 enzymes
- COX1: consitutive: specifically synthesize cytoprotective prostoglandins in the GI tract & formations of the thromboxane A2 platlet aggregation and hemostatsis system
- COX2: inducible and upregulated in inflammatory reponses
Treatment of NSAID related PUD
- what to use
- specifics of PPI
- specifics of H2RAs
- stop the NSAID (if possible)
- eridicate any H pylori (if also present)
- PPIs are first line treatment and DOC & for prevention of NSAID-induced ulcer
- H2RAs and sucralfate can be used, but PPIs are better
H2RAs: can be used high dose to heal and low dose to maintence prevent ucler formation
PPIs: -prazoles
Sucralfate and PUD NSAID related
Sucralfate
- used to create a physical barrier, NO role in supression of acid
- cannot be used prophylactically
- similar effectiveness as H2RA
- can be used for duodenal ulcers if the NSAID is stopped
- doesd 4x daily
Adverse Reactions (not systemically absobred)
- constipation
- nausea
- metallic taste
- aluminum toxicity possible if renal failure
if taking H2RA also – need to wait 30 mines between them
Risk Factors for Developing NSAID induced PUD
role of NSAIDS and COX2
- age > 65
- using ASA, corticosteroids or anticoags.
- on dual platlet thearpy = aspirin and clopidogrel
COX and NSAIDS
- nonselectives: traditional NSAIDS (COX1 and COX2)
- partial selective; celecoxib
- no avalible only COX2 meds in US
- asprin = salicylcate
Prevention of NSAID-induced Uclers
Long terms Maintenace
- PPIs: in their normal dosage is preferred
- Misoprostol: works well (acts as a syntehtic PGE, promotes mucosal defense) but lots of side effects (N/V/D, cramping) CANNOT USE IN PREGNANCY
- H2RAs: not recommned for prophylaxis
Long Term Maintenence
- acid suppression not needed: just treat the ulcer
- only the following pt. need long term thearpy
1. high risk with ulcer complications
2. long term NSAID use
3. failed H pylori eradication
