Week 4: GERD

esophagus

carries food, liquids, and saliva to stomach

LES (lower esophageal sphincter)

prevents reflux of gastric material from stomach; contracted at rest to prevent reflux and relaxes with swallowing to allow food to pass through

stomach

consists of parietal cells that secrete HCl, G-cells that secrete mucus, and chief cells that secrete pepsinogen

heartburn

retrosternal burning sensation; aka indigestion, acid regurgitation, sour stomach, or bitter belching; main symptoms of GERD

dyspepsia

symptoms originate from the gastroduodenal region; postprandial fullness, early satiation, epigastric pain, and epigastric burning that can be accompanied by belching, bloating, nausea, or vomiting

dyspepsia

heartburn can be a symptom of _________________, but ________________ does not have to include heartburn as a symptoms

mortality

GERD is rarely a cause of _______________

contracted

the LES under normal conditions is ____________, or tonic

relaxed

the LES while swallowing is _______________

relaxation

mechanisms for LES relaxation:

1) transient LES relaxations - stomach content can enter esophagus

2) increased intra-abdominal pressure -straining, coughing, eating

3) atonic LES

less

anatomical factors are _____________ likely to be primary etiology for GERD symptoms

hiatal hernia

occurs when a pouch forms where stomach comes through diaphragm, relaxing the LES and resulting in GERD

saliva

helps clear the esophagus; contains bicarbonate which counteracts acid in the stomach; production decreases with age and during sleep resulting in acid spending too much time in the esophagus

GERD

key factors of __________ development:

-LES Pressure

-Anatomic factors

-esophageal clearance

-mucosal resistance

-gastric emptying and increased pressure

-composition of refluxate

mucus

esophageal mucosa and submucosa contain _____________-secreting glands that protect the esophagus

secretion defect or repeat exposure to acid leads to cellular acidification and necrosis

pepsin

a pH of less than 2 leads to __________ activation and protein denaturation

dietary

__________ risk factors for GERD: fatty foods, spicy foods, chocolate, table salt, garlic or onions, mint, alcohol, caffeinated beverages, carbonated beverages, citrus fruit, tomatoes/juice

lifestyle

____________ risk factors for GERD: exercise, tobacco, obesity, stress, supine body position, tight-fitting clothing, pregnancy

medication

______________ risk factors for GERD: bisphosphonates, aspirin, NSAIDs, iron, potassium, nitrates, calcium channel blockers, benzodiazepines, tricyclic antidepressants

complications

_____________ of GERD:

-esophageal strictures

-Barrett's esophagus (precancerous cells)

-esophageal adenocarcinoma

-bleeding

brestbone

GERD presents as a burning sensation behind the ________________

1

GERD presents most frequently ______ hour after eating

regurgitation

flow of influxed material into the throat

water brash

hypersalivation; sudden filling of the mouth with clear fluid

cough

GERD may present as a chronic __________ without alternate explanation

bending over, lying down

______________ or ____________ may exacerbate the symptoms of GERD

self-treatment

Exclusions for ______________________ of GERD:

-frequent, severe, or nocturnal heartburn or while taking a H2RA or PPI

-difficulty or pain in swallowing

-vomiting blood or black material or passing black tarry stools

-chronic cough

-unexplained weight loss

-continuous nausea, vomiting, diarrhea

-chest pain accompanied by sweating, shortness of breath, or radiating to the shoulder, arm, neck, or jaw

2

children less than ____ should not use antacids

12

children less than _____ should not use H2RAs

18

children less than _____ should not use PPIs

alarm symptoms

________________________ for GERD:

-dysphagia

-odynophagia

-vomiting

-upper GI bleeding

-unexplained weight loss

-chest pain or trouble breathing

dysphagia

swallowing difficulties

odynophagia

painful swallowing

goals for GERD treatment

1) provide complete relief of symptoms

2) reduce recurrence of symptoms

3) prevent and manage unwanted effects of medications

pharmacologic

_______________________ treatment of GERD

-antacids

-H2RAs

-bismuth subsalicylate

-PPIs

antacids

Pharmacologic Effect: act as a buffering agent converting hydrogen ions to water and other compounds

indication: mild, infrequent heartburn (Episodic)

-pH >5 blocks pepsinogen conversion to pepsin

-increase LES pressure

magnesium

antacid that can be combined with hydroxide, carbonate, and trisilicate

aluminum

antacid that can be combined with hydroxide or phosphate

antacids

magnesium hydroxide, magnesium carbonate, magnesium trisilicate, aluminum hydroxide, aluminum phosphate; calcium carbonate, sodium bicarbonate

antacids (brands)

Alka-seltzer, Mylanta, Rolaids, Tums, Gaviscon

magnesium

____________ antacids have the fastest onset (liquid)

calcium carbonate

________________ antacids have the slowest onset (tablets)

magnesium, aluminum, sodium bicarbonate, calcium carbonate

order of antacids from fastest to slowest onset and shortest to longest duration

5

antacid onset is generally less than ____ minutes

20-30, 180

antacid duration is generally __________ minutes, and up to _______ minutes with food

magnesium

___________ antacid safety: dose-related diarrhea; excretion impaired in renal disease; should not be used in patients with CrCl

aluminum salts

____________ antacid safety: dose-related constipation; can build up in those with renal failure

calcium carbonate

_______________ antacid safety: may cause belching and flatulence

sodium bicarbonate

_________________ antacid safety: may cause belching, flatulence; should use with caution for sodium intake if patient has heart disease

2, 2

patients should be reevaluated if they are using antacids more than 2x per week or regularly for more than 2 weeks

antacid drug interactions

-tetracyclines

-quinolones

-levothyroxine

-amphetamines

-enteric-coated medications

-more!

2, 6

for most medications, it is safe to be on both concomitantly if the medication is separated either by ____ hours before the antacid or _____ hours after

H2RAs

pharmacologic effect: inhibits histamine type-2 receptor of the parietal cell decreasing fasting and food-stimulated gastric acid

H2RAs

indication: mild-moderate, infrequent, or episodic heartburn and for prevention of heartburn; at onset of heartburn or 30-60 minutes prior to anticipated event

30-60 minutes

onset of action for H2RAs

4-10 hours

duration of action for H2RAs

H2RAs

cimetidine (Tagamet), famotidine (Zantac, Pepcid)

reduced

all H2RAs should be administered at a __________ dose for those with CrCl

H2RAs

adverse drug events for _______________:

generally well tolerated with low incidence of adverse effects that include headache, diarrhea, constipation, dizziness, and drowsiness - rarely, reversible thrombocytopenia

climetidine

Tagamet

antiandrogenic

if cimetidine (Tagamet) is taken at high doses, it may have a ________________ effect (mess with male hormones)

CYP450

cimetidine (Tagamet) is an inhibitor of the __________ system: 3A4, 2D6, 1A2, 2C9

dangerous with phenytoin, warfarin, amiodarone, clopidogrel, tricyclic antidepressants, etc.

famotidine

Pepcid, Zantac

10-20 (max of 20 mg)

famotidine tablets have a strength of ____________ mg; max use of twice daily

30-60 minutes

onset of action for famotidine (Pepcid, Zantac)

famotidine, calcium carbonate, magnesium hydroxide

Pepcid Complete ingredients

PPIs

pharmacologic effect: irreversibly binds to and inhibits H-K ATPase pump (proton pump) blocking the final step of gastric acid secretion

PPIs

omeprazole (Prilosec), omeprazole sodium bicarbonate (Zegerid), lansoprazole (Prevacid), esomeprazole (Nexium)

PPIs

indication: treatment of frequent heartburn for patients with symptoms 2 or more days per week

2-3 hours

onset of action for PPIs

12-24

duration of action for PPIs

PPIs

short term ADEs for _________: headache, constipation, diarrhea

PPIs

long term ADEs for ___________: increased risk of hip, spine, and wrist fracture, increased risk for C. diff infection and community-acquired pneumonia, increased risk for CKD and dementia, and vitamin malabsorption

CYP2C19

drug-drug interactions for PPIs (lansoprazole, omeprazole, esomeprazole) inhibit ________________

methotrexate

interacts with PPIs, decreasing the ability to eliminate the drug which leads to toxicity

clopidogrel

interacts with PPIs, decreasing the ability to activate the drug (prodrug), leading to inefficiency

bismuth subsalicylate

Pepto Bismol; Kaopectate

bismuth subsalicylate

pharmacologic effect: unknown; may provide topical effect on stomach mucosa with some antimicrobial and anti-inflammatory effects

Bismouth Subsalicylate

indication: heartburn, dyspepsia, indigestion, nausea, and diarrhea

aspirin, NSAIDs

bismuth subsalicylate interact with ____________ and other ______________

bismuth subsalicylate

should be avoided in those with salicylate sensitivities and bleeding risks, as well as in children under the age of 12 and in pregnant women - risk of Reye's syndrome

bismuth subsalicylate

drug that may cause harmless and temporary dark stool and tongue

PPIs, Ca, Mg

while there is limited data on __________ during pregnancy (and lactation), ______ and _____ antacids are safe in recommended doses

Al, Mg, Ca

______, ______, and _______ antiacids are safe while lactating

famotidine

the safest H2RA to use while lactating