72. GERD + PUD Flashcards
Acidic gastric contents are normally prevented from backflow into the esophagus by a protective ring of muscle fibers called ___.
the lower esophageal sphincter (LES)
Typical GERD symptoms include ___
heartburn (daytime or nocturnal), hypersalivation and regurgitation of acidic contents into the mouth or throat
Less common symptoms: epigastric pain, nausea, cough, sore throat, hoarseness, chest pain (may be difficult to distinguish from cardiac pain)
Dx of GERD is based on ___
pt-reported symptoms, frequency (≥2x per week), and risk factors (e.g. family hx, diet and eating habits, sleep position)
If pt has alarm symptoms or there is a concern for more serious condition, ___ can be prefered. Pts who are refractory to GERD treatment may benefit from ____
endoscopy
24 hr esophageal pH monitoring
Drugs that can worsen GERD symptoms
Aspirin/NSAIDs
Bisphosphonates
Dabigatran
Estrogen products
Fish oil products
Iron supplements
Nicotine replacement thearpy
Steroiuds
Tetracyclines
Infrequent heartburn (< ___ times/week) can be treated with PRN OTC ____
<2x/week
OTC antacids or H2RAs
Frequent heartburn (≥2x/week) or severe GERD symptoms, ___ course of ___ is the initial treatment of choice and is used to heal any erosive esophagitis
8 week course of PPI
After 8 weeks of PPI initial treatment and GERD symptoms return, what is first line maintenance treatment?
PPI at lowest effective dose
Alt: H2RA if no erosive esophagitis and it relieves symptoms
Not recommended: metoclopramide or sucralfate
T/F: Since antacids do not require systemic absorption, they provide relief within minutes but duration is short (30-60 mins)
True
What is the concern of using antacids containing aspirin (e.g. Alka-Seltzer)
Increased risk of bleeding if used too frequently
Examples of antacids used in GERD
Calcium carbonate (TUMs)
Calcium carbonate + magnesium (Mylanta supreme)
Calcium carbonate + simethicone (Maalox, Advanced Maximum strength)
Magnesium hydroxide (Milk of Magnesia)
Magneiums hydroxide + aluminum + simethicone (Mylanta Maximum Strength)
Sodium bicarbonate/aspirin/citric acid (Alka-seltzer)
Dosing for antacids vary by product but many require administration ___ times per day
4-6 times per day
Concern with aluminum and magnesium in antacids used in GERD
Can accumulate with severe renal dysfunction (not recommended if CrCl<30)
Side effects of calcium containing antacids
Constipation
Others: bloating, belching
Side effects of aluminum containing antacids
constipation
Others: hypophosphatemia
Side effects of magnesium containing antacids
Loose stools (use with aluminum may counter-balance
___-containing antacids may be preferred in pregnancy
Calcium (Tums)
H2RA MOA
reversibly inhibit H2 receptors on gastric parietal cells, which decreases gastric acid secretion
Which H2RA comes as injection formulation?
Famotidine
What is the CrCl cut off for renal adj dosing with famotidine ?
CrCl <60
Warnings with H2RAs
Confusion, usually reversible (risk factors: elderly, severely ill, renal impairment)
Vit B12 deficiency with prolonged use (≥2 years)
Famotidine: QT prolongation with renal dysfunction
Side effects with H2RAs
HA, agitation/vomiting in children < 1 yo
Cimetidine (high doses): gynecomastia, impotence
of the H2RAs, why should cimetidine be avoided?
D/t drug interactions and side effects
Examples of H2RAs used for GERD
Famotidine (Pepcid AC, Zantac 360)
Cimetidine (Tagamet HB)
Nizatidine
Ranitidine (Zantac) – removed from market in April 2020
PPI MOA
Irreversibly bind to the gastric H+/K+-ATPase pump (proton pump) in parietal cells»_space; blocks gastric acid secretion
Which medication is most effective for GERD?
PPIs
Which PO PPIs should be taken before breakfast
Esomeprazoel (Nexium) - at least 60 min before breakfast
Lansoprazole (Prevacid, Prevacid SoluTab) - before breakfast (time not specified)
Omeprazole (Pilosec) - before breakfast (time not specified)
Omeprazole + sodium bicarbonate (Zegerid) - 60 min before breakfast (can control nocturnal symptoms if given at bedtime)
Which PO PPIs can be taken without regard to meals?
Dexlansoprazole (Dexilant) - without regard to meals
Pantoprazole (Protonix) - tab = without regard to meals, suspension = 30 min before meal
Rabeprazole (Aciphex) - tab = without regard to meals, capsul sprinkles = 30 min before meal
Examples of PPIs used in GERD
Dexlansoprazole (Dexilant)
Esomeprazole (Nexium) - comes in caps/tabs/injection/packet for oral suspension
Esomeprazeol + naproxen (Vimovo)
Lansoprazole (Prevacid) - comes in cap/ODT
Omeprazole (Prilosec) - comes in cap/tab/packet for oral suspension/ODT
Pantoprazole (Protonix) - comes in tab/injection/packet for oral suspension
Rabeprazole (Aciphex) - comes in tab/capsule sprinkle
Warnings with PPIs
C-diff associated diarrhea, hypomagnesemia, vit B12, deficiency with prolonged use ≥2 yrs, osteoporosis-related bone fractures with high doses or long-term (≥1 yr) use
PPIs may diminish therapeutic effect of clopidogrel - do not use omeprazole and esomeprazole (rabeprazole or pantoprazole have less risk)_
Others: acute interstitial nephritis (hypersensitivity reaction), cutaneous and systemic lupus erythematosus
IV Protonix - thrombophlebitis, SJS/TEN
Which H2RAs/PPIs come OTC?
H2RA: Cimetidine, famotidine
PPIs: esomeprazole, lansoprazole, omeprazole
Which PPIs come in ODT formulation?
Lansoprazole, omeprazole
Which H2RAs/PPIs come in oral solution/suspensions?
H2RA: cimetidine, famotidine, nizatidine
PPIs: lansoprazole // packets for suspension: esomeprazole, pantoprazole, omeprazole
Which H2RAs/PPIs come in injection formulations ?
H2RA: famotidine
PPIs: esomeprazole, pantoprazole
What is the concern with long-term PPI use?
Chronic changes in gastric pH»_space; can promote growth of microorganisms and increase risk of GI infections, including C. diff and possibly pneumonia (d/t reflux of gastric contents beyond oral cavity
Increase risk of osteoporosis and fractures
Beers Criteria recommends PPI not to be used beyond 8 weeks in elderly pts unless clear indication
Metoclopramide MOA
Dopamin antagonist
At higher doses, blockers serotonin receptors in the chemoreceptor zone of CNS which helps N/V
Enhances response to ACh in the upper GI tract»_space; increased motility, accelerated gastric emptying, and increased LES tone
When is metoclopramide (Reglan) taken?
before meals and at bedtime
What is CrCl cut off for renal dose adj for metoclopramide (Reglan)
CrCl <60 - decrease dose by 50% to avoid side effects including CNS/EPS side effects
Boxed warning for metoclopramide (Reglan)
Can cause tardive dyskinesia - higher risk with high doses, long-term treatment (>12 weeks),and elderly pts
Warnings with metoclopramide (Reglan)
EPS (including acute dystonia), Parkinsonian-like symptoms
Others: rare neuroleptic malignant syndrome (NMS), depression, suicidal ideation
Avoid use in pts with Parkinson disease
Side effects with metoclopramide (Reglan)
Drowsiness
Others: restlessness, fatigue, HTN, pro-arrhythmic, diarrhea
Which meds should be avoided when taking H2RAs or PPIs?
Delayed release formulation of Risedronate (Atelvia)
Avoid with PPIs: Erlotinib, rilpivirine, and velpatasvir/sofosbuvir (Epclusa)
Drugs that require acidic gut (absorption decreased by antacids, H2RAs, and PPIs)
Antiretrovirals: rilpivirine (NNRTI), atazanavir (PI)
Antivirals: ledipasvir, velpatasvir/sofosbuvir
Azole antifungals: Sporanox (itraconazole caps), ketoconazole, posconazole oral suspension
Cephalosporins (oral): cefpodoxime, cefuroxime
Iron products
Meselamine
Risedronate DR
TKI: dasatanib, erlotinib, pazopanib
Oral drugs/drug classes that antacids bind
Antiretrovitals (INSTIs): bictegravir, dolutegravir, elvitegravir, raltegravir
Bisphosphonates
isoniazid
Levothyroxine
Mycophenolate
Quinolones
Sotalol
Steroids (esp budesonide)
Tetracyclines
When using H2RAs, use caution with CNS depressants (esp in elderly) d/t risk of additive ____ . Use lower doses in pts with renal impairment
delirium, dementia, and cognitive impairment
Cimetidine is an ___ of CYP450 enzymes (e.g. 2C19, 3A4, 1A2)
inhibitor
Avoid use with dofetilide, use caution with other drugs including amiodarone, CCBs, clopidogrel, phenytoin, SSRIs, theophylline, and warfarin
All PPIs inhibit CYP ____. Most are weak inhibitors but ___ and ___ are moderate inhibitors (can decrease effectiveness of ____ through inhibition)
Can increase levels of citalopram, phenytoin, tacrolimus, voriconazole, and warfarin. Do NOT use PPIs with nelfinavir.
2C19
Esomeprazole and omeprazole
Clopidogrel - avoid esomeprazole and omeprazole use with this drug
Do not use metoclopramide in pts receiving meds for __ disease (antagonistic effect)..
Do not use in combo with anypsychotics d/t increased risk of adverse effects
When used in combo with SSRIs, SNTIs, and TCAs, monitor for ____
Parkinsons disease
Serotonin syndrome, EPS, and NMS
3 most common causes of PUD are ___
H. pylori-positive ulcers (most common)
NSAID induced ulcers
Stress ulcers (occur in critically ill and mechanically-ventilated pts)
Describe H. pylori bacterium
Spiral-shaped
pH sensitive
gram-negative
S/sx of PUD
Primary symptom: dyspepsia, gastric pain that can feel like gnawing or burning sensation in the middle or upper stomach
Other symptoms: heartburn, belching, bloating, cramping, nausea, anorexia
T/F: If ulcer is duodenal (usually caused by H. pylori), pain is typically worse 2-3 hrs after eating; eating food or taking antacids lessens the pain.
True
T/F: With gastric ulcers, eating generally lessens the pain
False - worsens the pain
Diagnostic tests for H.pylori include ____.
PPIs, bismuth, and abx should be d/c ____ prior test to avoid false neg test.
urea breath test (UBT) which detects CO2 produced by the bacterial
Fecal antigen test which detects H. pylori in stool
2 weeks
What is American College of Gastroenterology (ACG) recommended drug treatment for H. pylori infection?
Bismuth quadruple therapy x10-14 days: Bismuth + metronidazole + tetracycline + PPI BID
Concomitant therapy x10-14 days (if clarithromycin resistance rates <15% and no prior exposure to macrolide): amoxicillin + clarithromycin + metronidazole + PPI
Clarithromycin triple therapy x14 days (if clarithromycin resistance rates are <15%): amoxicillin (metronidazole if PCN allergy) + clarithromycin + PPI BID
What is in bismuth quadruple therapy for H. pylori treatment?
Bismuth quadruple therapy x10-14 days
Bismuth 300mg QID
metronidazole 250-500 QID
tetracycline 500mg QID
PPI BID
or use 3-in-1 combo + PPI: Pylera (bismuth 420mg + metronidazole 375mg + tetracycline 375mg) QID + PPI BID
What is in clarithromycin triple therapy for H. pylori treatment?
Clarithromycin triple therapy x14 days (if clarithromycin resistance rates are <15%):
amoxicillin 1000mg BID (metronidazole if PCN allergy)
clarithromycin 500mg BID
PPI BID (or esomeprazozle 40mg daily)
or use 3-in-1 combo: Prevpac (amoxicillin + clarithromycin + lansoprazole)
What is in concomitant therapy for H.pylori treatment?
Concomitant therapy x10-14 days (if clarithromycin resistance rates <15% and no prior exposure to macrolide):
amoxicillin 1000mg BID
clarithromycin 500mg BID
metronidazole 500mg BID
PPI
concern with alcohol use and bismuth quadruple therapy
Alcohol use - do not use metronidazole
Concern with pregnancy/children and bismuth quadruple therapy
Do not use tetracycline during pregnancy or in children < 8yo
Concern with salicylate allergy and bismuth quadruple thearpy
Do not use bismuth subsalicylate
NSAIDs with selective inhibition of COX-2 (e.g. ___) have decreased ___ risk but increased ___ risk compared to non-selective NSAIDs
celecoxib
decreased GI risk but increased CV risk
NSAIDs that approach the selectivity of celecoxib are. _____
meloxicam, nabumetone, diclofenac, etodolac
Combo products specifically marketed to reduce risk of NSAID-induced ulcers include _____
naproxen/esomeprazole (Vimovo)
Ibuprofen/famotidine (Duexis)
Diclofenac/misoprostol (Arthrotec)
____ is approved for secondary prevention of CV and cerebrovascular events in pts at risk for aspirin-associated ulcers
Yoprala (aspirin/omeprazole)
If NSAID-ulcer develops, what do you recommend?
treat with PPI for 8 weeks and d/c NSAIDs
If PPIs cannot be used, high-dose H2RA or sucralfate are other options
Misoprostol MOA
Prostaglandin E1 analog that replaces gastro-protective prostaglandins removed by NSAIDs
Sucralfate MOA
sucrose-sulfate-aluminum complex and. can interact with albumin and fibrinogen to form physical barrier over an open ulcer»_space; protects ulcer from further insult by HCl acid, pepsin and bile, allowing healing
Boxed warning for misoprostol (Cytotec)
Abortifacient - do not use to decrease NSAID-induced ulcers in females of childbearing potential unless capable of adhering to effective contraceptive measures
Arthrotec (misoprostol/diclofenac): NSAIDs increase risk of serious GI events and CV disease
Side effects of misoprostol
Diarrhea, abd pain
Sucralfate (Carafate) side effects
Constipation
When is sucralfate (Carafate) taken
Before meals (empty stomach) and bed time
Why is sucralfate (Carafate) difficult to use?
D/t binding interactions (separate antacids by 30 mins and take other drugs 2 hrs before and 4 hrs after)
metoclopramide is most commonly used for ____
gastroparesis
