Dyspepsia & GERD Flashcards
What is dyspepsia?
epigastric pain or discomfort originating from upper GIT
-an umbrella term to describe many possible sx and causes
What is functional dyspepsia?
dyspepsia where no abnormalities are found
What is gastroesophageal reflux disease?
reflux of gastric contents into the esophagus
-described as heartburn
What is peptic ulcer disease?
an ulcer formed in the gastric or duodenal mucosa
-may have symptoms similar to dyspepsia/GERD
What are the potential mechanisms which cause functional dyspepsia?
gastric motility and compliance
visceral hypersensitivity
H.pylori infection
altered gut microbiome
duodenal inflammation
psychosocial dysfunction
What are the many possible causes of dyspepsia?
normal finding (functional dyspepsia)-70%
GERD-15%
gastric ulcer-2%
gastric erosions-6%
duodenal ulcer-2.9%
gastro-esophageal malignancy-0.2%
What are the risk factors for dyspepsia?
dietary indiscretion
medications
H.pylori infection
anxiety
IBS
smoking or alcohol use
True or false: there is a strong association between sex, age, and socioeconomic status with the risk for dyspepsia
false
What are some examples of drug-induced dyspepsia?
bisphosphonates
iron
NSAIDs
potassium
What are the many different symptoms that qualify as dyspepsia?
epigastric pain or discomfort
fullness or early satiety
nausea
upper abdominal bloating
excessive burping or belching
heartburn and regurgitation
>1 month duration of symptoms
What are the alarm symptoms of dyspepsia?
VBAD:
-vomiting
-bleeding/anemia
-abdominal mass or unexplained weight loss
-dysphagia or odynophagia
chest pain
choking
Describe the systemic approach to take in patients with dyspepsia.
- evaluate other possible causes
-cancer, malabsorption, diabetes, IBD, medications, etc - upper GI location?
- new onset symptoms (other than reflux/heartburn) > 50 (++>60) or red flag symptoms?
- NSAID use?
- reflux or regurgitation as main symptom?
- H.pylori present?
What is the pathophysiology of GERD?
reflux of stomach acid contents into esophagus, possibly leading to reflux (non-erosive) esophagitis or erosive esophagitis
What are the many potential causes of GERD?
defective lower esophageal sphincter
increased intra-abdominal pressure
hiatal hernia
impaired esophageal peristalsis
delayed gastric emptying
excessive gastric acid production
What are the risk factors for GERD?
obesity
pregnancy
family history
smoking
increased age (>65)
hiatal hernia
stress and anxiety
medications
diet
What are some drug-induced causes of GERD?
anticholinergics
benzodiazepines
opioids
What are some dietary contributors to GERD?
over-eating
fatty foods
chocolate
alcohol
carbonated drinks
acidic juices
everyone has their own different triggers
What are the primary symptoms of GERD?
heartburn and regurgitation
What are some other findings and atypical extra-esophageal symptoms of GERD?
other findings:
-belching, hypersalivation, non-cardiac chest pain
atypical extra-esophageal symptoms:
-chronic cough
-throat clearing
-SOB or wheezing
-laryngitis
-oropharyngeal symptoms
-dental erosions
Differentiate mild and moderate/severe GERD.
intensity:
-mild: low
-mod/severe: high
interference with ADLs:
-mild: no
-mod/severe: yes
frequency:
-mild: <3/wk
-mod/severe: >3/wk
duration:
-mild: <6 months
-mod/severe: >6 months
nocturnal symptoms:
-mild: no
-mod/severe: yes
complications:
-mild: no
-mod/severe: yes
What are the potential complications of GERD?
esophagitis
esophageal stricture
esophageal erosions
Barretts esophagus
esophageal cancer
What are the red flags of GERD?
VBAD
choking
chest pain
How is GERD diagnosed?
based on symptoms after ruling out other causes
-those with typical sx do not require invasive testing
-trial course course of pharmacologic therapy helpful
Who are the candidates for upper endoscopy?
new onset sx (other than reflux/heartburn) >50 or red flag sx
any alarm features
refractory GERD
at risk for Barretts esophagus
What are some “other” diagnostic tests for GERD?
barium swallow
esophageal manometry
ambulatory esophageal pH monitoring
What are the goals of treatment for GERD?
relieve symptoms
promote healing of injured mucosa
prevent and treat complications
prevent recurrence
avoid issues with long-term use of pharmacotherapy
Which patients should consider non-pharmacologic treatment for GERD?
should be considered in all patients
What are some lifestyle changes that can demonstrate benefit for GERD?
evidence based:
-lose and maintain IBW
-stop smoking
-elevate head of bed
others that may help but not evidence based:
-smaller meals
-trigger food avoidance
-remain upright 2-3h after eating
-avoid eating 3h before bed
-avoid tight clothing
Provide an overview of the pharmacologic treatment for GERD.
as needed or on-demand treatment:
-alginates
-antacids
-H2RAs
-PPIs (slow acting, not great prn)
scheduled treatment:
-H2RAs
-PPIs
adjuncts:
-domperidone
-metoclopramide
anti-reflux surgery
What is an example of an alginate?
sodium alginate (included in Gaviscon)
What are the indications for alginates?
mild, intermittent, post-prandial GERD
What are the contraindications to alginates?
none
What is the MOA of alginates?
forms a viscous “raft” that floats within the stomach
How should alginates be administered?
~1h after eating
What is the onset and duration of alginates?
rapid onset and short duration <1h
What are the safety concerns of alginates?
bloating
flatulence
belching
What is the efficacy of alginates for GERD?
better than placebo, worse than other agents
What are examples of antacids?
aluminum hydroxide
magnesium hydroxide
magnesium trisilicate
calcium carbonate
sodium bicarbonate
What are the indications for antacids?
mild, infrequent, post-prandial GERD
What are the contraindications to antacids?
severe renal impairment
-unless dialysis
What is the MOA of antacids?
neutralizes stomach acid
inhibits pepsin generation
binds to bile acids
What is the onset and duration of antacids?
rapid acting
short duration of action
How should antacids be administered?
chew 2-4 tablets up to QID (max 8-16 tablets)
30-60 min after a meal and/or bedtime
What are the common side effects of antacids?
aluminum: constipating
magnesium: laxative effect
calcium: well tolerated
What are the serious side effects of antacids?
aluminum: bone demineralization, neurotoxicity, hypophosphatemia
magnesium: hypermagnesemia
calcium: hypercalcemia, alkalosis
What are the drug interactions of antacids?
chelation with many drugs: space antacid 1h before or 2h after
-ex: tetracyclines, fluoroquinolones, iron, bisphosphonates, levothyroxine
impairs absorption of pH sensitive drugs
-dabigatran, HIV meds
What is the efficacy of antacids for GERD?
limited evidence
slight reduction in symptom severity and frequency
better than placebo, inferior to other agents
possible role of add-on therapy in severe cases
What are examples of H2RAs?
cimetidine
famotidine
ranitidine
nizatidine
What are the Health Canada indications for H2RAs?
all: GERD tx and duodenal/gastric ulcer tx and prevention
famotidine: GERD maintenance of remission
What are the off-label indications for H2RAs?
functional dyspepsia
prophylaxis of NSAID-related ulcers
nocturnal GERD
H.pylori infection
What are the contraindications to H2RAs?
none
What is the MOA of H2RAs?
parietal cells in stomach pump H+ ions into gastric lumen
block the H2 receptors prevent pump activation
reduction in basal and stimulated gastric acid secretion
What is the onset and duration of H2RAs?
acid secretion inhibition begins within 1-3h
meal stimulated secretion inhibited for 3-5h
nocturnal suppression lasts 8-13h
How should H2RAs be administered?
30-60 min prior to a meal
What are the common side effects of H2RAs?
extremely well tolerated
HA, VD, drowsiness
Which H2RA is not well tolerated?
cimetidine is poorly tolerated
-higher rates of HA, VD, drowsiness
-gynecomastia
What are the drug interactions of H2RAs?
all: decrease absorption of drugs requiring acidity
cimetidine weakly-moderately inhibits 1A2, 2C19, 2D6, 3A4
Describe the efficacy of H2RAs for GERD.
effective for mild or food-triggered GERD
more effective than antacids, less effective than PPIs
safe and cheap option to consider in mild GERD
has a role in step-down therapy
significant tachyphylaxis demonstrated
True or false: H2RA combination with PPIs is much more effective than either alone
false
What are examples of PPIs?
rabeprazole
omeprazole
pantoprazole
esomeprazole
lansoprazole
dexlansoprazole
What is the difference between pantoprazole sodium and magnesium?
sodium is older, magnesium is newer
magnesium theoretically gives longer duration and help for nocturnal sx
not interchangeable
What are the indications for a PPI?
treatment of GERD symptoms
symptomatic relief and healing of erosive esophagitis
symptomatic relief and healing of duodenal and gastric ulcers
prevention of NSAID-induced ulcers
use in H.pylori eradication regimens
treatment of ZES
What are the contraindications to PPIs?
none
What is the MOA of PPIs?
directly inhibit proton pump to prevent gastric acid secretion
-prodrugs designed to become activated in duodenum
-absorbed and concentrate in parietal cell
-only works on actively secreting proton pumps
What is the onset and duration of action of PPIs?
initial doses will result in suboptimal gastric inhibition
daily use for at least 3-5 days results in maximal inhibition
proton pump recovery takes 24-48h after d/c
How should PPIs be initiated?
at standard dosing regimen
How should PPIs be administered?
30 minutes before breakfast
What are the indications for double dose PPIs?
if standard dose not effective after adequate trial (~4-8wks)
initial presentation of erosive esophagitis
ulcers or GI bleed indications
H.pylori eradication
What is the duration of therapy for PPIs?
standard or double dose for 4-8 weeks, then d/c or step-down
What are the common side effects of PPIs?
well tolerated
dyseugia
nausea
headache
dizziness
diarrhea
constipation
rash/pruritis
What are the serious side effects of PPIs?
C.difficile infection
microscopic colitis
hypomagnesemia
fractures
fundic gland polyps
B12 deficiency
pneumonia
gastric cancer
mortality increase
Describe C.diff infections as a serious side effect of PPIs.
risk increased with concomitant antibiotics
also increases recurrence of C.diff
may also increase risk of salmonellosis and campylobacter
Describe microscopic colitis as a serious side effect of PPIs.
lansoprazole may be worst of the PPIs
risk increased when combined with NSAIDs
Describe hypomagnesemia as a serious side effect of PPIs.
can lead to many complications (muscle, dizziness, confusion)
risk increases with duration
Describe fractures as a serious side effect of PPIs.
possible fracture risk increase
calcium carbonate requires an acidic environment for best absorption
dietary calcium or supplements taken with food unaffected
Describe fundic gland polyps as a serious side effect of PPIs.
polyps in stomach (generally benign and harmless)
long term use (>5yrs) = 4x risk increase
short term (<1yr) = no risk
resolves with withdrawal
Describe B12 deficiency as a serious side effect of PPIs.
absorption reduced by lower acidity environment
B12 supplements NOT affected
Describe pneumonia as a serious side effect of PPIs.
conflicting evidence
unlikely to be associated
Describe gastric cancer as a serious side effect of PPIs.
dose and duration dependent
NNH is high
What are the drug interactions of PPIs?
all: reduces absorption of drugs requiring acidity, substrates of CYP
lanso: mild reduction in theophylline and mycophenolate
omep and esomep modify lvls of many drugs
dex, pant, rab have very little enzyme effects
Describe the efficacy of PPIs.
all PPIs equally effective
more effective than H2RAs and antacids
What are examples of prokinetics?
domperidone
metoclopramide
What is the MOA of prokinetics?
dopamine antagonists stimulate gastric motility
What is the main indication for prokinetics?
GI motility disorders
What is the role of prokinetics in GERD?
unclear
-minor role in functional dyspepsia
What is the onset and duration of prokinetics?
within 30 min
lasts 1-2h
How should prokinetics be adminstered?
15-30 min before meals and bedtime
What are the contraindications to metoclopramide?
GI obstruction, perforation or hemorrhage
seizure disorder
extra-pyramidal symptoms
Parkinsons
What are the contraindications to domperidone?
GI obstruction, perforation or hemorrhage
long QT interval
electrolyte disorders
use with potent 3A4 inhibitors
What are the side effects of metoclopramide?
common:
-drowsiness (~50%)
-muscle weakness
-headache
-dizziness
-confusion
serious:
-pseudoparkinsonism
-EPS symptoms
-tardive dyskinesia
-gynecomastia
-hyperprolactinemia
What are the side effects of domperidone?
common:
-dry mouth
-mild headache
serious:
-QT prolongation
-gynecomastia
What are the drug interactions of the prokinetics?
metoclopramide:
-2D6 substrate, watch for strong inhibitors
-opposes effect of anti-Parkinson agents
-enhances effect/toxicity of antipsychotics
-enhances effect/toxicity of SSRIs/TCAs
domperidone:
-3A4 substrate, watch for strong inhibitors
-QT prolonging agents
What are the two approaches to treatment of GERD?
step-up: delays getting sx under control
-lifestyle–>prn therapy–>scheduled H2RA–>scheduled PPI
step down: preferred
-scheduled course of PPI for specific duration
-then find lowest strength option to control sx
When should we re-assess GERD symptoms for someone on a PPI?
at 4-8 weeks
if sx resolved, trial d/c is appropriate
-if sx recur > 3 months after d/c, begin another 4-8wk course
-if sx recur < 3 months after d/c, treat again but investigate
if sx improved, but not resolved, continue for another 4-8 wks
-consider dose increase or switch to different PPI
When is GERD considered refractory?
failure on 2 month course of once daily PPI
symptoms recur within 3 months of PPI discontinuation
~25% of patients will be refractory
What are the main reasons for failure of GERD therapy?
medication timing and adherence
differences in PPI metabolism
weakly acidic or alkaline reflux
reflux hypersensitivity
alternative diagnoses
What is the stepwise management of refractory GERD?
- reassess for any alarm sx
- ensure adequate duration attempted
- ensure proper adherence and administration
- reinforce lifestyle and dietary modification
- optimize OR switch current PPI
- advanced diagnostics
- add adjunct tx (alginates, antacids, H2RA hs, prokinetic)
- surgery
What is one of the most over-used medication classes?
PPIs
True or false: most patients will remain symptom free after successful initial course of a PPI
true
What should be attempted with a PPI after a 4-8 week trial?
de-prescribe
-if long term therapy, most should attempt to deprescribe once per year
Who are the candidates to recommend deprescribing?
mild-moderate GERD who responded to therapy
PUD treated for proper duration
asymptomatic for 3 consecutive days
H.pylori eradication successful
Which strategy might be more successful for deprescribing a PPI?
tapering PPI may be more successful than abrupt d/c
-decrease dose each week as stepwise as possible
-may dose qod to help with taper
-initiating H2RA may help with taper
True or false: functional dyspepsia is easily treated
false
What is the management of functional dyspepsia?
- PPI OD for 4-8 wks
- H.pylor testing/eradication
- switch/add-on TCA
- switch/add-on prokinetic
When do we consider treatment for GERD in pediatrics?
only consider if complications
-poor weight gain
-blood in stool or vomit
-intense irritability temporally related to food intake
What are the warning signs of a more serious pathology in pediatric GERD?
forceful vomiting
abdominal tenderness or distention
fever
systemic signs
What is the management of pediatric GERD?
- if no warning signs, parent reassurance
- assess lifestyle as a trigger
- trial of acid supp for two weeks (PPI>H2RA)
- if improvement, continue therapy x 2-3 months
- if no improvement, begin invasive diagnostics
What are the safety concerns of acid suppression in pediatrics?
acid rebound
diarrhea
pneumonia
Which approach is preferred for GERD in pregnancy?
step-up
Which GERD medications should be avoided in pregnancy/lactation?
sodium bicarbonate
magnesium trisilicate
Which GERD medications show no harm in pregnancy/lactation?
no harm indicated with H2RAs and PPIs
-prefer lansoprazole, omeprazole, pantoprazole
pantoprazole preferred in lactation
What are the primary symptoms that must be present that would allow a pharmacy to prescribe for GERD?
heartburn and regurgitation
What are some examples of drug-induced esophagitis?
doxy/tetracyclines
clindamycin
NSAIDs/ASA
bisphosphonates
potassium tablets
What are the symptoms of drug-induced esophagitis?
similar to GERD
What can increase the risk of drug-induced esophagitis?
lying down after taking medications
swallowing pills with saliva only
inadequate water intake
esophageal dysmotility
hiatus hernia
esophageal strictures
large pills
bed ridden
