GERD & PUD Flashcards
What type of cell secretes HCl
Parietal cells
HCl is secreted in response to what 3 physiologic stimuli?
- ACh
- Histamine
- Gastrin
Which of the 3 physiologic stimuli is most important clinically?
Histamine
What type of transmitter is histamine?
Paracrine
What does histamine bind?
H2 receptors on basolateral membrane of parietal cells
H+ ions are actively secreted in exchange for….
K+ (by Na+/K+ pump on surface of parietal cells)
Acid secretion is driven by what nerve
Vagus n.
What is the most frequent GI condition encountered in outpt. setting
GERD (20% of population)
Sx of GERD
- Heartburn & regurg (classic sx)
- Dyspepsia (early satiety, gutt rot)
- Chest pain
- Belching
- Dysphagia
- Voice changes
- Chronic cough
Complications of GERD
- Barrett’s esophagus
- Strictures
- Bleeding
What are examples of alarm symptoms?
Dysphagia, GI bleed, anemia, wt. loss, persistent vomiting
What diagnostic tool is used to evaluate alarm symptoms?
Endoscopy
What other patient population is endoscopy recommended for?
Pts at high risk for complications
- Those who do not respond to 4-8 wk trial of PPI
- Men >50 w/ chronic GERD (>5yr) who have additional RF for Barrett’s (e.g. obesity, hiatal hernia)
What are examples of lifestyle modifications used in GERD mgmt?
- Avoid lying down for at least 2 hours after eating or drinking
- Elevating HOB
- Wt. loss
What lifestyle modification is no longer recommended for GERD pt?
Avoiding foods thought to trigger reflux e.g. chocolate, caffeine, alcohol, spicy foods
Tx regimen for mild, infrequent GERD
Antacid or H2RA
Tx regimen for severe, frequent GERD OR those whose sx are inadequately controlled on antacid or H2RA
PPI
How many weeks of PPI therapy is recommended prior to de-escalation?
8 wks
In what populations is PPI de-escalation not recommended?
- Pt. on chronic ASA therapy
- Barrett’s esophagus
Pts. on a PPI (PO QD) who continue to have sx, may benefit from what alteration to their tx regimen?
- BID therapy
- Switching to another PPI
What is recommended for pt. who still have noctural sx despite BID PPI therapy?
Addition of H2RA therapy
Pts who have recurrent sx ater stopping a PPI may respond to what?
- Another course of tx
- On-demand PPI tx
What type of tx regimen is recommended for the healing of erosive esophagitis?
PPI x8wks (almost all pt. will have relapse within 6mo of stopping tx, most will require indefinite tx)
Most antacids are comprised of various salts including:
- Al(OH)3
- CaCO3
- Mg(OH)2
Common antacid preparations
- Aluminum hydroxide + magnesium hydroxide
- Calcium carbonate + magnesium hydroxide
- Calcium carbonate
Antacid MOA
- Neutralizes gastric acidity (↑ gastric pH)
- Inhibits proteolytic activity of pepsin when gastric pH >4
Clinical indications for antacids
PRN for dyspepsia/GERD
Drug interactions with antacids
- ↓ TCC & FQ absorption (form nonabsorbable complexes)
- ↓ absorption of various agents (itra/ketoconazole, Fe2+, digoxin, phenytoin) d/t “alkalization” of stomach
Al(OH)3 ADRs
- Hypophosphatemia
- Aluminum intoxication
- Constipation
Aluminum intoxication could cause what in CKD pts.?
Encephalopathy, seizure, coma
CaCO3 ADRs
- Constipation
- Milk-Alkali syndrome
What is Milk-Alkali syndrome?
HA, nausea, irritability, weakness, hypercalcemia, metabolic alkalosis, & hypophosphatemia w/ large doses or in CKD pts.
Mg(OH)2 ADRs
- Hypermagnesemia
- Laxative effects
What is sucralfate?
Aluminum hydroxide complex of sucrose
Sucralfate MOA
Forms a complex by binding with positively charged proteins in exudates; viscous paste-like/adhesive provides protective coating
Clinical indications for sucralfate
- GERD/PUD (minimally used)
- NSAID-induced mucosal damage
- Prevention of stress ulcers
- Suspension used topically for tx of stomatitis d/t CA chemo/other causes
Interactions for sucralfate
↓ absorption of itra/ketoconazole, digoxin, phenytoin, warfarin, theophylline, TTC, FQ
- Take other meds 2 hrs before
Why is taking medications 2 hrs before sucralfate difficult?
Sucralfate is a QID drug
Sucralfate ADRs
- Constipation
- Aluminum toxicity in CKD pts
Examples of 1st gen H2RAs
- Cimetidine
- Ranitidine
Examples of 2nd gen H2RAs
- Famotidine
- Nizatidine
What H2RA is the FDA investigating in regards to NMDA content?
Ranitidine
- Products have been pulled from the market
H2RA MOA
Inhibit gastric secretion by blocking histamine receptors on parietal cells
- Reduction in basal gastric acid secretion > food-stimulated after a single dose
Are H2RAs good for regular use or prn use
PRN
What H2RA should we encourage the use of?
Famotidine
Clinical indications for H2RAs
- Dyspepsia/GERD/PUD
- SUP in critically ill pt.
- Gastric hypersecretory states (PPI >)
Decreased GI acidity with H2RAs may lead to what?
HAP/VAP & CDI
Drug interaction with H2RAs
↓ absorption of itra/ketoconazole, digoxin, phenytoin, Fe2+
Which H2RA is a weak/moderate inhibitor of almost every isoenzyme?
Cimetidine
- Use discouraged because of this
H2RA ADRs
- Acid rebound (stopping med leads to a surge; mitigated with taper, antacids for breakthrough)
- Confusion in cognitively impaired/demented elderly pt.
Cimetidine ADRs
- ED (libido)/gynecomastia (chronic use)
- Drug fever
- Agranulocytosis
Examples of PPIs
- Omeprazole*
- Esomeprazole
- Pantoprazole*
- Rabeprazole
- Lansoprazole*
- Dexlansoprazole
- what we use for the most part
What PPIs are available IV>
- Esomeprazole
- Pantoprazole
Why don’t we use the IR formulation of omeprazole that’s buffered by NaHCO3?
Too much Na+
PPI MOA
Suppresses gastric basal & food-stimulated secretion by inhibiting parietal cell H+/K+ ATP pump
When should PPIs be taken/administered?
30-60 minutes before 1st meal
Why should PPIs be taken/administered after a prolonged fast?
Amount of H-K-ATPase present in parietal cell is greatest after a prolonged fast
Clinical indications for PPIs
- GERD ( role for chronic dz w/ mild-mod sx; intermittent vs. “on-demand” vs continuous)
- PUD +/- bleeding - standard of care!
- SUP in critically ill pt.
- Gastric hypersecretory states - standard of care!
- H. pylori infection
Indications for intermittent PPI dosing for GERD pt.?
Occasionally heart burn sx (every 3rd day)
Indications for “on-demand” PPI dosing for GERD pt.?
For new change in disease course
Indications for continuous PPI dosing for GERD pt.?
Pt. w/ complications (e.g. Barrett’s, strictures)
Concerns with PPI use that contribute to decision making
- ↑ CDI
- CAP/HAP
- ↑ fx risk in PM women & pt. >50yo OR pts. on high dose for >1yr -> ↓ Ca+ absorption
- Hypomagnesia, iron or B12 deficiency (anemia?) r/t long-term use (>1yr)
What is our goal if we put a PPI on board?
Use the lowest effective dose for the shortest duration possible
Which PPIs are available OTC?
- Omeprazole
- Esomeprazole
- Lansoprazole
Do PPIs differ clinical for sx relief, esophagitis/ulcer healing etc?
nah
There is a risk of tolerance developing with H2RAs or PPIs?
H2RAs
What can we considering monitoring in a pt. on a PPI?
Mg+! @ baseline AND periodically in pt. on long-term therapy (>2wks) or those on diuretics, digoxin
PPI use should be avoided in what two populations?
- Pt. on drugs that carry a known risk of TdP
2. Pt. with long QT syndrome
Do PPIs cause QT prolongation?
NO! The drug itself does not BUT it manipulates the absorption of cations
If extended drug therapy is indicated in a pt. that is taking a QT prolonging drug, what should monitor?
- Mg+
- QT interval
PPIs are substrates of CYP___ & CYP___
CYP2C19; CYP3A4
Most PPIs are moderate inhibitors of CYP___
CYP2C19
What PPIs should we use concomitantly with CYP2C19 substrates, such as phenytoin & clopidogrel?
- Pantoprazole*, lansoprazole, dexlansoprazole
- Omeprazole & esomeprazole may be problematic
Omeprazole moderately inhibits CYP___
CYP2C9 (caution w/ warfarin, phenytoin)
Other drug interactions w/ PPIs
- ↓ absorption of itra/ketoconazole, digoxin, phenytoin, Fe2+/Ca+/Mg+/B12
- ↓ MTX clearance
PPI ADRs (generally)
- Nosocomial inf
- Anemia
- Fx
- AIN -> CKD w/ long term use
What drug is a synthetic analog of prostaglandin E1?
Misoprostol
Misoprostol MOA
Gastric antisecretory agent w/ protective effects on GI mucosa
Use of misoprostol is CONTRAINDICATED in what pt. population?
Pregnant women (stimulates expulsion of ~products of conception~)
- Category X
- r/o possibility prior to use + contraception during use
Clinical indications fro misoprostol
- Prevention of NSAID-induced ulcers
- Treatment of PUD
- Various obstetric indications
Why os misoprostol not 1st line for tx of PUD?
Requires multiple daily doses & ADRs
Misoprostol ADRs
Diarrhea & abd pain
Why is heartburn so common in pregnancy? (up to 80%)
Prostaglandin mediated ↓ in LES tone
5 steps to treating GERD/PUD in pregnancy
Step 1: lifestyle modifications Step 2: antacids Step 3: sucralfate (if antacids fail) Step 4: H2RA Step 5: PPI considered (persistent sx on H2RA)
“Recommended” antacids in pregnancy
- Aluminum hydroxide + magnesium hydroxide
- Calcium carbonate
- regarded as safe, but watch for ADRs
Antacids to avoid in pregnancy
- Mg+ trisilicates
- Sodium bicarb
What harm might Mg+ trisilicates cause to a fetus?
Nephrolithiasis, hypotonia, respiratory distress (chronic use/high doses)
What harm might sodium bicarb cause in pregnancy?
Materal/fetal metabolic alkalosis & fluid overload
What drugs/classes are category B?
- Aluminum hydroxide + magnesium hydroxide
- Sucralfate
- H2RA (ranitidine > *most data)
- PPIs (except omeprazole - C)
Examples of supplemental iron
- Ferrous sulfate (65-100 elemental iron/tab)
- Ferrous fumarate (65-100 elemental iron/tab)
- Ferrous gluconate (35 elemental iron/tab)
When should iron supplement be taken?
Best absorbed on empty stomach, but may be better tolerated w/ food (if GI upset occurs)
Iron supplements may cause ↓ absorption of….
- Bisphosphonates
- Levodopa
- LT4
- FQs
- TTCs
What other meds ↓ absorption of iron supplements?
- Ca+/Al/Mg+ containing antacids
- H2RAs
- PPis
Dosing of iron:
100-200mg/day of ferrous sulfate or ferrous fumarate
- Start 1 tab/d, titrate up to BID or TID over 1-2 wks if tolerated
What do we monitor 1x/mo in iron-deficient pt. on supplements?
Hgb
H. pylori can cause gastric inflammation & has been associated with what other pathologies
Gasritis, PUD, gastric adenocarcinoma, MALT
Eradication of H. pylori….
- Promote gastric healing
- Prevents recurrence of ulcers
- ↓ incidence of gastric CA
Testing for H. pylori
- Noninvasive: urea breath, stool antigen, serology
- Invasive: endoscopy w/ bx
How to choose a regimen for tx of H. pylori
- Prior macrolide exposure?
- Allergies?
- Dosing convenience
- Cost?
What does TRIPLE therapy for H. pylori consist of?
PPI + clarithromycin + amox or metronidazole
Why is triple therapy falling out of favor?
Clarithromycin resistance
At what parameter of clarithromycin resistance would be an indication to move to quadruple therapy?
Clarithromycin resistance >15%
- Local resistance patters, ABX resistance testing NOT widely available -> make the switch to quadruple therapy anyway
What does concomitant QUADRUPLE therapy for H. pylori consist of?
PPI + clarithromycin + amox + metronidazole or tinidazole
How often is concomitant QUADRUPLE therapy dosed?
BID
What does bismuth QUADRUPLE therapy for H. pylori consist of?
PPI + bismuth + TTC + metronidazole or tinidazole
How often is bismuth QUADRUPLE therapy dosed?
QID
How long do we treat w/ quAdruple therapy?
10-14d
What do we do post-quadruple therapy treatment?
“Cure documentation”
What can be used sometimes for dyspepsia or to distinguish GERD & CP in the ED?
GI cocktails
- Do NOT rely on to r/o CP
What constitutes a GI cocktail?
Liquid antacid + viscous lidocaine +/- antispasmodic (e.g. Donnatal)
Adding Donnatal), lidocaine, or both to an antacid….
Does NOT seem work better for dyspepsia than an antacid alone (liquid antacid alone is recommended)
No good evidence that magic mouthwash is better than….
Homemade salt & sodium bicarb rinse
Two magic mouthwash recipes
- Viscous lidocaine + diphenhydramine + liquid antacid (1:1:1)
- BLM kit: Benadryl + Licocaine + Maalox (Al + Mg hydroxide) + simethicone ($$$)
Pt. ed for magic mouthwash
- Swish & SPIT for oral ulcers
- Swish & SWALLOW for pharyngeal or esophageal ulcers
- Use q4-6hrs PRN
- Hold in mouth for 1-2min
- Don’t eat or drink for 30 min after
