kale PUD

what are peptic ulcers

open sores created on the digestive system epithelium, due to inadequate mucus protection --> acid corrosion

1. duodenal

2. gastric= antrum of stomach

have ulcer rates been increasing or decreasing

duodenal ulcers: overall decline

gastric ulcers: less dramatic decline (aging pop, increased NSAID use)

-> women mortality rate INCREASING

-> men mortality rate DECREASING

describe 4 regions of stomach and 4 secreting cells

cardia, fundus, body, pylorus

1. parietal cells: HCl

2. chief cells: pepsinogen

3. mast cells: histamine

4. G cells: gastrin

pathogenesis of peptic ulcers

aggressive vs defensive factors

aggressive: acid, pepsin, gastrin, bile acid

defensive: mucosal blood flow, bicarb, cellular regeneration, prostaglandins

(remember prostaglandins were actually aggressive factor in GERD bc lower LES pressure!!)

where are drug induced peptic ulcers more likely to occur (stomach vs duodenum)? which drugs?

gastric

drugs: NSAIDs, adrenocorticosteroids, chemo

where are infection-induced ulcers more likely to occur (gastric or duodenal)? which organisms?

duodenal

H. pylori, CMV

RISK FACTORS FOR PUD

(not direct causes)

1. cigarette smoking= decreased response to H2RAs, ulcer reoccurrence

2. alcohol: mucosal irritant, bleeding

3. caffeine: gastric acid stimulant, dyspepsia

4. spicy food: dyspepsia

5. stress: ulcer pain and disability, induces behavior risks (smoking)

how does epigastric pain present in PUD

- usually nocturnal

- DU: episodic and clusters

- pain may radiate to back

antacids provide relief

food might relieve or increase pain

what effect can PUD have on bp/hr/hgb/hct

bleeding causes decreased intravasc volume

- lower bp

- higher HR

- lower hgb/hct [<13/50% ish]

radiography dx

- uses barium and xray to see ulcer crater

- can result in false negative for small ulcers

esophago-gastro-duodeno-graphy (EGD)

- use endoscope to see GI mucosa directly

- MOST ACCURATE AND CONCLUSIVE. not gold standard tho (histology)

what is the most accurate diagnostic test for PUD? gold standard?

most accurate=

esophago-gastro-duodeno-graphy (EGD)

gold standard= histology/ microbio examination for H/ pylori

histology dx for PUD

GOLD STANDARD

-microbio examination for various strains

- patchy distribution of HP results in false negatives

a __________ diagnostic tool is used to test for antibiotic resistance

culture

urease (biopsy)

CLO test

campylobacter-like organism test (CLO test)/ urease biopsy

TEST OF CHOICE DURING ENDOSCOPY

-rapid screening test to detect the presence of the bacterium Helicobacter pylori

- HP ammonia causes a color change= rapid results show active infection

t/f: a CLO test/ urease biopsy only shows an inactive infection

false. it shows active infection bc HP produce ammonia which leads to color change

what is the test of choice for H. pylori during endoscopy

urease (biopsy)

CLO test

dx tests:

_________= gold standard

________= most accurate and conclusive

__________= test of choice at endoscopy; H. pylori active infection

_________= test to confirm HP eradication [non endoscopic]

histology= gold standard

EGD= most accurate and conclusive

urease (biopsy)= test of choice at endoscopy; H. pylori active infection

urea breath test= test to confirm HP eradication

which test can be used to confirm HP eradication? describe what it entails

urea breath test (non-endoscopic)

- ingest urea with labeled carbon: C13 nonradioactive or C14 radioactive

- HP produces urease which will break down the urea, and you will find labeled C in breath via CO2

no bacteria= no labeled C in breath

which non-endoscopic technique can be used to tests for the presence of HP but will NOT differentiate btwn an active or inactive infection

serology= tests for Igs against HP [will be in blood for 6-12months]

what is shock

drop in bp <90 systolic

chronic complications of PUD

- GI bleeding (melena, hematemesis, shock)

- perforation (ulcer eroded through lining)

- gastric outlet obstruction (scarring of pylorus)

- gastric cancer (NOT direct complication)

t/f: gastric cancer is a direct complication of PUD

false

H. pylori characteristics

gram neg spiral

flagella

acid labile!!! needs pH>4 to survive

secretes urease to form NH3 and CO2 from acid

class 1 carcinogen

infects gastric antrum and is carried into duodenum via peristalsis

t/f: H. pylori primarily infects the duodenum

false. infects gastric antrum and is carried into duodenum via peristalsis. most duodenal ulcers are H. pylori cases

non-pharm measures for HP PUD

1. avoid irritating foods (spicy, fried)

2. avoid caffeine and alcohol

3. stop smoking

4. stress management

what were old 2017 guidelines for h. pylori PUD

MOC= metronidazole, omeprazole, clarithromycin

COA= clarithromycin, omeprazole, amoxicillin

for 14 days

levofloxacin triple therapy

levofloxacin 500mg qd, amoxicillin 1000mg bid, PPI bid for 10-14 days

not fda approved, and low quality of evidence

fluoroquinolone sequential therapy

PPI + amoxicillin for 5-7 days

then

PPI + fluoroquinolone + metronidazole for 5-7 days

low quality of evidence!!

fluoroquinolones

-floxacin

macrolide

-mycins

t/f: in 2024 guidelines, clarithromycin and levofloxacin (fluoroquinolone) is no longer first line

true. antibiotic resistance

optimized bismuth quadruple therapy

indication and dose

recommended first line for HP PUD

- used in pts with PCN allergy or macrolide exposure

PPI BID

Bismuth subsalicyate 300 or subcitrate 120-300 QID

tetracycline 500mg QID

metronidazole 500mg TID or QID

can pt with aspirin allergy be given optimized bismuth quadruple therapy

yes. switch bismuth subsalicylate 300mg to bismuth subcitrate 120-300mg

rifabutin triple therapy for tx naive

NOT FOR PCN ALLERGY (amoxicillin)

omeprazole 20-40mg BID

amoxicillin 1000mg BID

rifabutin 50-300mg QID

4 capsules TID of combo Talicia

vonoprazan dual therapy

vonoprazan 20mg BID

amoxicillin 1000mg TID [NOT FOR PCN ALLERGY]

for 14 days

vonoprazan triple therapy

vonoprazan 20mg BID

amoxicillin 1000mg BID [NOT FOR PCN ALLERGY]

clarithromycin 500mg BID

for 14 days

reserve for clarithromycin sensitive strains!

for treatment naive pts with H. pylori infection,

recommended first line?

2 alternates?

1. optimized bismuth quadruple

2. rifabutin triple

2. vonoprazan dual

2. vonoprazan triple

for a pt previously on PPI-clarithromycin triple or non-optimized BQT with persistent HP infection, what is next tx

-optimized BQT

- rifabutin triple

[high dose PPI or PCAB dual if above arent options]

for tx-experienced pts who underwent antibiotic susceptibility testing, what would you give for clarithromycin and levofloxacin-sensitive strains

- clarithromycin triple [omit if clarithromycin resistant]

- optimized BQT

- rifabutin triple

- levofloxacin triple [omit if levofloxacin resistant]

for tx-experienced pts who underwent antibiotic susceptibility testing, what would you give for clarithromycin and levofloxacin-resistant strains

- optimized BQT

- rifabutin triple

- high dose PPI or PCAB dual

for treatment-experienced pts with H. pylori infection,

what are 2024 tx options for no antibiotic sensitivity

- optimized bismuth quadruple

- rifabutin triple

possibly vonoprazan dual if above arent options

for treatment-experienced pts with H. pylori infection,

what are 2024 tx options for pts with proven antibiotic sensitivity

- optimized bismuth quadruple

- rifabutin triple

- vonoprazan triple (clarithro sensitive)

- levofloxacin triple (levo sensitive)

possibly vonoprazan dual if above arent options

what is the only possible tx regimen for HP PUD for those with penicillin allergy

optimized bismuth quadruple

rifabutin triple therapy for pts who have already tried BQT

PPI BID

amox 1000mg BID or TID

rifabutin 50-300mg QID

orrrrrrrr

combo Talicia 4 caps TID

levofloxacin triple therapy for pts w known levofloxacin-sensitive HP and when BQT and rifabutin failed

PPI BID

Levofloxacin 500mg QD

amox 1000mg BID or metro 500mg BID

can you interchange antibiotics for HP PUD tx

no

can you interchange bismuth preparations for HP PUD tx

no

can you interchange PPIs and H2RAs in HP PUD tx

- may interchange PPIs

- may sub PPI in place of H2RA but u CANNOT use H2RA in place of a PPI

t/f: probiotics are a low cost alternative that may increase HP eradication rates

true

describe how NSAIDs correlate to erosions/ulcers

locally= direct damage to mucosa bc acidic

systemic= NSAIDs inhibit COX which is needed for prostaglandin synthesis (defensive factor)

COX 1 vs COX 2

COX1: protective PG that are always expressed (stomach, intestines, kidney, platelets)

COX2: stops PG at site of infalmmation

-> so using COX2 selective NSAIDs is less damaging

t/f: aspirin is more selective for COX2 than naproxen

false. naproxen is more selective for COX2, followed by ibuprofen, and then aspirin

celecoxib

Celebrex

NSAID that is selective for COX2

what did the VIGOR and APPROVE trials/studies determine regarding selective COX 2 inhibitors? CLASS trial?

less GI toxicity but higher chance of MIs

CLASS trial-> long term data showed no difference btwn celecoxib and other NSAIDs in rate of ulcer complications. so gastric effects still occur

t/f: typical PUD symptoms do NOT occur in NSAID ulcers

true. may have ASYMPTOMATIC bleeding and perforation

there is poor correlation btwn sx and endoscopic findings

RISK FACTORS FOR NSAID INDUCED GI TOXICITY

-Age >65

-previous peptic ulcers/ ulcer related complications

- high dose or a lot of NSAID use

- aspirin

- chronic disorders: cardiovasc, rheumatoid arthritis

- HP infection

- cigs and alcohol

DRUGS:

NSAID with aspirin, bisphosphonates, corticosteroids, anticoags, antiplatelets, SSRIs

the concomitant use of which drugs is a risk for NSAID induced GI toxicity

NSAID with low dose aspirin

bisphosphonates (alendronate)

corticosteroids

anticoags

antiplatelets

SSRIs

NSAID induced ulcers treatment

1. stop NSAID-> give H2RA or PPI

2. if cant stop-> give PPI

strategies to minimize NSAID injury

- take w food/antacid

- enteric coated aspirin

- use tylenol

misoprostol

moa

dose

prostaglandin analog used to prevent NSAID-induced DU and GU

MOA: enhances mucus, bicarb, and blood flow. some antisecretory

dose: 200mcg QID w food

misoprostol CIs

1. PREGNANT

- stimulates uterus== abortions

2. Mg coated antacids

- increases diarrhea and cramps

tx used to prevent NSAID ulcers

1. misoprostol (prostaglandin analog)

2. concomitant PPIs

t/f: PPIs are superior to H2RAs in preventing NSAID induced ulcers

true

how should the following pts be treated according to GI risk [over 60, use of asp/steroids/antiplatelet and coag/ SSRIs]

and CV risk [CV, diabetes]

(summary)

low GI and low CV: nonselective NSAID

high GI and low CV: nonselective NSAID and PPI [may sub for celecoxib if hx of ulcer]

low GI and high CV: naproxen

[ if on aspirin then naproxen + PPI]

high GI and high CV:

1. avoid NSAIDs

2. naproxen + PPI

3. celecoxib + asp + PPI

what NSAID is recommended if pt has high CV risk

naproxen

(can add PPI if taking aspirin or has high GI risk)

-> low CV risk, give nonselective NSAID

t/f: naproxen is preferred over non-selective COX2 inhibitors in CV

true

omeprazole and esomeprazole inhibit CYP_____ and affects these meds:

CYP2C19

phenytoin, warfarin, carbamazepine, diazepam [increases effect]

clopidogrel [attenuates/decreases]

which antiviral can PPIs reduce and why

atazanavir-> pH dependant

risk of rebleeding

- over 65yo

- shock (BP <90)

- poor overall health

- initial low Hb

- melena/ emesis

- transfusion requirement

why is acid suppressant therapy recommended with NSAIDs for high GI risk pts? optimal pH?

pepsin inhibits clot formation

gastrin impairs ulcer healing

platelets aggregate at pH 7.4

impaired at pH <6!!

t/f: tolerance only occurs with H2RAs and NOT PPIs (need more of med over time)

true

dosing of PPI for bleeding peptic ulcers

pantoprazole or esomeprazole 80mg IV bolus then 8mg/hr

PPIs are formulated to be released when pH is

pH is above 7 (intestine)

exposure to gastric acid degrades the PPI

PPIs can lower absorption of drugs such as ______ by increasing gastric pH

ketoconazole, itraconazole, cefpodoxime proxetil

FDA warning for PPIs

1. increases risk of fractures of hip, wrist, and spine

- pts at risk of osteoporosis should take VItD/ Ca supplement

- monitor bone status

2. C. diff diarrhea

3. pneumonia

t/f: both H2RAs and PPIs are associated with pneumonia risk

true

t/f: vonoprazan therapies are at least as effective as PPI-based therapies, and can be given to pts on drugs metabolized by CYP2C19 or those who failed on PPI

true

what is sucralfate approved for

tx of acute and maintenance DU

[NOT approved for GU or NSAID GI injury]

sucralfate moa

aluminum salt that binds to ulcers forming a protective barrier, inhibits pepsin's actions, stimulates PGs

sucralfate dosing for active DU and maintenance

active: 1gm QID or 2gm BID for 4-8 weeks

maintain: 1gm BID

take on empty stomach!!! can bind to protein and phosphates in diet

sucralfate ADEs

constipation, hypophosphatemia, increased Al concentrations in renal impairment

which drugs should be taken 2hrs before sucralfate

- tetracycline

- digoxin

- theophylline

- fluoroquinolones (floxacin)

abx tolerability

all:

drug interactions:

pregnancy:

children:

other:

all: diarrhea, c. diff colitis, hypersensitivity

unpleasant taste: metro and clarithro

drug intrxns: metro and clarithro

AVOID in pregnant: clarithro and TCN

AVOID in children: TCN

t/f: tetracyclines, macrolides, and fluoroquinolones are known for QT prolongation

false. macrolides (mycins) and fluoroquinolones (floxacins) yes. not tetracyclines