kale GERD

what are the aggressive and defensive factors for GER

aggressive (makes it worse):

1. gastric acid, pepsin

2. bile salts, pancreatic enzymes

3. prostaglandins (lower LES pressure)

defense:

1. LES pressure increase

2. esophageal clearance

3. mucosa

4. increased gastric emptying

explain cyclic nature of GER

incompetent LES causes reflux and delayed clearing which causes esophagitis which makes LES more incompetent

RISK FACTORS FOR GERD

intra abdominal pressure= pregnancy, obesity, ascites

lower tone= surgery, hiatal hernia, chalasia, nasogastric intubation

other: scleroderma, cigarette smoking

foods causing lower LES pressure and increased GERD

- fatty meals

- garlic

- carminatives (peppermint, spearmint)

- onions

- chocolate

- chilli peppers

- caffeine (coffee, cola, tea)

medications causing decreased LES pressure and increased GERD

-ANTIcholinergics (remember Cholinergics actually constrict LES)

- barbiturates (ex: phenobarbital)

- nicotine, caffeine/theophylline, ethanol

- CCB (amlodipine, nifedipine), nitrates

- progesterone/ estrogens

- dopamine

- tetracycline

foods that are DIRECTLY irritating to esophageal mucosa

spicy foods, tomato juice, orange juice, coffee

meds that are DIRECTLY irritating to esophageal mucosa

alendronate, iron, aspirin, quinidine, NSAIDs, KCl

risk factors for POOR OUTCOMES/COMPLICATIONS in GERD

Age: over 40

Sx for 3 years

dysphagia (hard to swallow)

bleeding, anemia

weight loss

los angeles classifications of reflux esophagitis

LA grade A: best, mucosal break <5mm

LA grade D: worst, break >75%

test of choice for diagnosing GERD

ambulatory pH monitoring

- monitoring device inserted in esophagus, if pH drops then reflux is occuring

-costly; used for pts with atypical sx

barium esophagogram

- shows motility abnormalities, hiatal hernia, esophageal stricture

-not helpful in diagnosing GERD with no esophageal damage

[use amb pH monitoring]

endoscopy

-useful for dx of esophagitis or Barrett's

-not helpful in diagnosing GERD with no esophageal damage [use amb pH monitoring]

lifestyle modifications for GERD management

1. elevate head of bed

2. modify diet= avoid spice, fatty, mint, chocolate, caffeine

- eat high protein small meals

- avoid eating before lying down

3. avoid tight fitting clothes

4. stop smoking

5. avoid agents that lower LES tone

antacids for GERD

MOA

rank from most to least potent

MOA: neutralize acid, bind bile acids and salts, bind pepsin

- relieve symptoms

- liquids preferred

from most to least potent: calcium carbonate (Tums)> sodium bicarb> Mg> Al

antacids

drug interactions may result from:

- formation of insoluble complex

- adsorption

- increase gastric pH (some drugs need acidity-iron)

- increase urinary pH (basic drugs less excreted)

pros and cons of antacids for GERD management

pros:

-OTC, rapid symptom relief

cons:

- frequent dose regimen

- costly to use regularly

-ADE: constipation (Al), diarrhea (Mg), electrolyte changes

- drug interactions: tetracyclines, iron, quinolones, antifungals

which drugs do antacids interact with, and require dose separation

tetracycline

iron= lower absorption

quinolones (floxacins)

antifungals (azoles)

which ingredients in antacids can lead to diarrhea and which lead to constipation

Mg= diarrhea

Al, Ca= constipation

alginic acid

use in GERD:

MOA:

Gaviscon

= both lower sx AND endo healing

MOA: reacts w saliva to form viscous solution that acts as mucosal barrier

H2RAs

MOA:

reversibly bind to H2 in parietal cells

- decreases cAMP, decreases activation of proton pump, lowers H+ secretion== increased gastric pH

- also decreases secretion of pepsinogen!

which agents stimulate the parietal cell to secrete H+ via increased cAMP and calcium

histamine= stimulates cAMP

acetylcholine= releases calcium

gastrin= releases calcium

==== activates proton pump

H2RA agents available OTC (generic and brand)

cimetidine (Tagamet)

nizatidine (Axid)

famotidine (Pepcid, Zantac 360)

[ranitidine/zantac was removed bc of NMDA levels]

H2RAs OTC dosing (not prescription!!)

cimetidine:

famotidine:

ranitidine-> not available anymore

over 12 years old

cimetidine (tagamet): 200mg tab w water [max 2]

famotidine (pepcid): 10mg tab w water [max 2]

famotidine (pepcid(: 20mg tab w water [max 2]

which H2RAs may cause diarrhea? which one doesnt have major GI side effects?

cimetidine= diarrhea

nizatidine= diarrhea, constipation, flatulence

famotidine== XXX

which H2RAs have hepatic ADR's? dont?

cimetidine= hepatic fibrosis

nizatidine= increased LFTs

famotidine= XXX

CNS and endocrine ADRs for H2RAs

dizziness, headache, somnolence (drowsy), decreased libido

H2RAs drug interactions mechanisms and drug examples

1. inhibits renal tubular secretion

== creatinine, theophylline, procainamide

2. increases gastric pH, lower absorption for drugs that need acid

== ketoconazole, itraconazole, cefpodoxime

3. inhibit CYPs

== warfarin, theophylline, phenytoin, carbamazepine, propranolol, lidocaine, quinidine

C>N>F

compare H2RAs based on which one has most drug interactions

cimetidine>nizatidine> famotidine

- famotidine has least amount of side effects

- cimetidine known to increase creatinine in blood (may present as AKI)

which PPIs are available and which are OTC vs RX only

OTC:

-lansoprazole (Prevacid)

- omeprazole (Prilosec)

- esomeprazole (Nexium)

RX:

- dexlansoprazole (Dexilant)

- pantoprazole (Protonix)

- rabeprazole (Aciphex)

PPIs MOA

-sulfonamide group on PPI IRREVERSIBLY bind to proton pump and inhibits final step in acid secretion

- reduces secretion of pepsinogen slightly

- increases serum gastrin

mayy develop carcinoid tumors bc of increased gastrin

how are PPIs activated

exposure to gastric acid degrades the PPI, so theyre formulated to be released only when pH> 7 (in intestines)

which PPIs have an interaction with warfarin and what is it

omeprazole and esomeprazole

== inhibit CYP2C19 therefore increasing warfarin's effects-> bleeding risk

PPIs drug interactions

1. decreased absorption bc increased pH

== ketoconazole, itraconazole, cefpodoxime

2. OMEP AND ESOMEP inhibit 2C19

== warfarin!! diphenhydramine, carbamazepine, diazepam

3. reduce oral bioavailability of atazanavir (for HIV)

zegerid

omeprazole/sodium bicarbonate

GERD

-> take combo product on empty stomach or hour before meals

when should PPIs be taken

once a day: 15-30mins before breakfast

twice a day: separate second dose from morning by 10-12hrs

[this is differential!! PUD is always once a day, GERD can be 2x a day]

FDA warnings regarding PPIs

- risk of fractures (give Vit D and calcium)

- risk of C. diff diarrhea

- pneumonia

OTC dosing for PPIs

omeprazole:

Zegerid:

lansoprazole:

esomeprazole:

omeprazole (Prilosec): 20.6mg [1 tab 30mins before breakfast for 14 days]

omep 20mg/ sodium bicarb 1100mg [Zegerid]: 1 cap 1 hr before breakfast for 14 days

lansoprazole (Prevacid) 15mg: 1 cap 30mins before breakfast for 14 days

esomeprazole (Nexium): 20 mg: 1 cap 30mins before breakfast for 14 days]

-> max 1 per day for OTC

compare antacids, H2RAs, and PPIs based on onset and duration of relief

onset:

1. antacids= less than 5 mins

2. H2RAs= 30-45mins

3. PPIs= 2-3hrs

duration of relief

1. antacids= 20-30mins (shortest but PROLONGED w food)

2. H2RAs= 4-10hrs

3. PPIs= 12-24hrs (longest onset but longest duration)

if pt is experiencing

episodic heartburn treat with->

heartburn >2 days per week treat with->

episodic

1. lifestyle/diet modifiers

2. antacid or alginic acid or H2RA

frequent more than 2 days per week

1. lifestyle/ diet modifiers

2. PPI for 14 days or H2RA as needed

when do you know you can stop an OTC PPI? when can you repeat the regimen?

stop if heartburn has resolved after the 2 weeks of PPI (if not-> referral)

repeat regimen every 4 months if needed, or continue H2RA as needed

EXCLUSIONS TO SELF TREAT GERD/HEARTBURN

1. heartburn more than 3 months

2. heartburn persists with use of OTC H2RA or PPI (14 days)

3. severe heartburn and dyspepsia

4. nocturnal heartburn

5. difficulty/pain when swallowing

6. vomiting blood or black tarry stools

7. chronic hoarseness, wheezing, coughing, choking

8. unexplained weight loss

9. N/V/ diarrhea

10. chest pain w sweating, radiating to arm/neck/jaw, SOB

AGES:

- children less than 2 (for antacids)

- children less than 12 (for H2RAs)

- children less than 18 (for PPIs)

- adults >45 with new onset dyspepsia

age exclusions for GERD self treatment

- children less than 2 (for antacids) "Tums Two"

- children less than 12 (for H2RAs) "Tagamet Twelve

- children less than 18 (for PPIs)

- adults >45 with new onset dyspepsia

5 targets for pharm intervention for GERD

1. esophageal clearance

-> bethanechol, cisapride

2. esophageal mucosal resistance

-> alginic acid, sucralfate

3. LES pressure

-> bethanechol, metoclopramide, cisapride

4. gastric emptying

-> metoclopramide, cisapride

5. gastric acid

-> antacids, H2RAs, PPIs

indication for tx of GERD with Rx PPIs

- severe erosive esophagitis (LA grades C or D)

- maintenance tx of GERD

what is the initial dosage regimen for RX PPIs for 4-8 weeks? what about for unresponsive pts- for how long?

initial 4-8 weeks:

omeprazole, esomeprazole, rabeprazole= 20mg qd

lansoprazole= 15-30mg qd

dexlansoprazole= 30mg qd

pantoprazole= 40mg qd

INCREASE DOSE TO TWICE DAILY in unresponsive pts for 4-16 weeks total

adverse rxns for RX PPIs

- headaches

- diarrhea, ab pain, nausea

- bacterial overgrowth

risk of carcinogenesis is not supported

when are RX PPIs the drug of choice?

- moderate to severe GERD

- pts not responding to H2RAs

- pts with complicated symptoms (Barrets, strictures)

PPIs are usually first line tx for GERD

how can PPIs be deprescribed in eligible pts (uncomplicated GERD/ not severe)

1. wean down to lowest effective dose (if sx continue use PPI as needed, or add on H2RAs/antacids for nocturnal sx)

2. reduce twice daily PPI to once daily

which pts are INELIGIBLE to be de-prescribed off of PPIs

1. complicated GERD: severe erosive esophagitis, esophageal ulcer, strictures

2. Barret's esophagus

3. eosinophilic esophagitis

4. idiopathic pulmonary fibrosis

5. high risk of GI bleed

what can occur after PPI discontinuation and how should the pt be educated

rebound acid hypersecretion

-pts can use PPIs, H2RAs, antacids to control sx short term

BUT if sx last >2 months after stopping, they may require continued PPI therapy

t/f: if rebound acid hypersecretion lasts for more than 2 weeks in pts who stopped PPIs, they may require continued PPI therapy

false. if lasts more than 2 months

t/f: data has shown that all PPIs are equally effective in GERD

true

t/f: data has shown that PPIs are just as effective as H2RAs in treating GERD

false. data has shown that PPIs are more effective in healing. H2RAs are only recommended as adjunctive therapy to PPIs or nocturnal breakthrough symptoms

[remember nocturnal cant be self treated tho!]

vonoprazan moa

PCAB=potassium competitive acid blocker

REVERSIBLY binds to proton pump

how is vonoprazan metabolized

CYP 3A4 mainly

2B6, 2C19, 2C9, 2D6

-> has longer half life and also a lot of potential drug interactions

t/f: vonoprazan is similar in effectiveness to PPIs in healing erosive esophagitis and improving GERD sx

true

which warnings come with vonoprazan

1. gastric malignancy

2. nephritis

3. c. diff diarrhea

vonoprazan drug interactions

1. CYP 2C19: attenuates/lowers clopidogrel effectiveness

2. lowers absorption of drugs that need acid= atazanavir, nelfinavir, rilpivirine

bethanechol

moa:

dosage regimen:

ADE:

CI:

cholinergic agonist increases LES tone

dosage: 25mg po QID

ADE: pain, diarrhea, urinary frequency, salivation, sweating, lacrimation

CI: asthma, COPD, PUD

NOT RLLY USED BC POOR EFFICACY AND ADRs

metoclopramide

MOA:

dosage:

dopamine antagonist that increases LES tone and accelerates gastric emptying

dosage: 10mg po ac and hs

metoclopramide

ADEs:

drug interactions:

CIs:

efficacy:

ADEs: CNS, extrapyramidal rxn, diarrhea, rash

drug interactions: altered absorption

CIs: Parkinsons, use of other dopamine antagonists or anticholinergics

efficacy: poor efficacy, not rlly used

sucralfate

MOA:

dosage:

mucosal protection, adsorbs to damaged mucosa, binds pepsin and bile salts

dosage: 1gm 1hr before meals (ac) and qhs [suspension!!]

sucralfate

ADE:

drug interactions:

clinical efficacy:

ADE: constipation, hypophosphatemia, aluminum absorption in renal failure pts

drug interactions: adsorbs meds, decreases their absorption

clinical efficacy: NOT FDA APPROVED FOR GERD but helps some

indications for surgery for GERD tx

1. sx dont improve with tx

2. stricture formation

3. severe bleeding

4. dysplastic epithelium

5. pulmonary complications

what is the general approach to treating a pt with mild infrequent sx (<2 days a week) with no signs of erosive esophagitis

1. lifestyle changes

2. antacids, alginic acid, H2RAs prn

3. H2RAs in divided doses

how can erosive esophagitis be treated

REFERRAL

1. lifestyle

2. PPIs

3. combo PPI with promotility agent (remember CNS effects tho! not good for elders)

maintenance tx for GERD

(most relapse after 6 months if dont maintain)

1. lifestyle

2. acid suppression with PPIs

3. refractory pts: combo PPI and promotility

how can pediatrics be treated for GERD

liquid formulations

1. RX PPIs: omeprazole, lansoprazole, esomeprazole, pantoprazole

2. H2RAs: cimetidine, famotidine

but remember you cant SELF treat the following:

- children less than 2 (for antacids) "Tums Two"

- children less than 12 (for H2RAs) "Tagamet Twelve

- children less than 18 (for PPIs)

which drugs are excreted in breastmilk?

H2RAs and PPIs

(risk vs benefit)

which drug is the first line choice in pregnancy

famotidine

(PPIs can still be used when clinically indicated)

notes for treating geriatrics for GERD

- may think this is normal part of aging

- decreased motility is common problem

- metoclopramide and H2RAs may cause confusion/delirium bc of their CNS effects

when should single dose PPI therapy be assessed to see if it worked? what if it DID work?

4-8 weeks

if symptoms got better:

1. wean to lowest effective dose

2. continue on lowest dose or switch to prn

pts on chronic PPI for _______ should be offered reflux testing to determine requirement for lifelong therapy

1 year

when should single dose PPI therapy be assessed to see if it worked? what if it DID NOT work?

4-8 weeks

didnt work:

1. assess compliance

2. increase dose to 2x a day PPI [not fda approved tho]

------> assess again

if still not improved

1. EGD and wireless pH testing OFF of the PPI

what is the overall tx algorithm for GERD (summary)

weeks 1-8:

weeks 9-16: (if sx persist)

weeks 17+: (if sx persist)

weeks 1-8

1. start with PPI qd

2. use H2RA for nocturnal breakthrough

----> if sx improve, dc or taper

weeks 9-16

1. increase PPI to BID, change PPI, or split PPI dose

2. use H2RA for nocturnal breakthrough

3. add alginate antacid for sx control

weeks 17+

1. continue HD PPI

2. use H2RA for nocturnal breakthrough

3. add ons: baclofen, metoclopramid if concomitant gastroparesis

which drug can be added on for GERD tx with gastroparesis

metoclopramide (note CNS sedation in elders)

how should dose be altered for ultrarapid metabolizers

increase starting dose by 100%

-> may be given in divided doses

for rapid or normal metabolizers, dose may be increased by __________ for tx of H. pylori infection and erosive esophagitis

50-100%

how should dose be altered for intermediate/poor metabolizers

initiate standard dose

- consider 50% reduction for chronic therapy (>12 weeks)

why may asthma worsen in the presence of GERD

GERD can trigger asthma symptoms through vagus nerve stimulation and bronchoconstriction

pt MR presented to doctor with erosive esophagitis. she has been prescribed pantoprazole and has not had any other sx since. is she eligible for discontinuation?

no, she has erosive esophagitis and needs to stay on it long term

remember exclusions for de-prescribing:

1. complicated GERD: severe erosive esophagitis, esophageal ulcer, strictures

2. Barret's esophagus

3. eosinophilic esophagitis

4. idiopathic pulmonary fibrosis

5. high risk of GI bleed