GERD & PUD Flashcards

1
Q

What is GERD?

A
  • Gastroesophageal reflux disease
  • Lower esophageal sphincter (LES) is a protective ring of muscle fibers that prevent backflow of gastric contents into esophagus.
  • Persons with GERD have reduced LES pressure (muscle tone) where backflow of gastric contents into esophagus can occur
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2
Q

What are symptoms of GERD?

A
  • Heartburn
  • Hypersalivation
  • Regurgitation
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3
Q

How do you diagnose GERD?

A
  • Based on patient-reported symptoms, frequency (>=2 times per week) and risk factors
  • Endoscopy can be performed if a patient has alarm symptoms or concern fore a more serious condition
  • Patients who are refractory to GERD treatment may benefit from 24-hr esophageal PH monitoring
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4
Q

List key drugs that can worsen GERD symptoms

A
  • Aspirin/NSAIDs
  • Bisphosphonates
  • Dabigatran
  • Estrogen products
  • Fish oil products
  • Iron supplements
  • Nicotine replacement therapy
  • Steroids
  • Tetracyclines
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5
Q

What are the treatment principles for GERD?

A

Infrequent heartburn (< 2 times/week):
* Lifestyle modifications;

- Weight loss (if overweight or recently gained weight)

- Elevate the head of the bed with foam wedges or blocks
- Avoid eating high fat meals within 2-3 hours of bedtime
- Avoid foods/beverages that trigger reflux; caffeine, chocolate, acidic/spicy foods, carbonated beverages
  • Antacids and H2RAs (PRN)

Initial drug treatment:
* PPI once daily for 8 weeks; can increase to twice daily If partial response or nocturnal symptoms are present

  • There are no major differences in efficacy between the available PPIs
  • Stop treatment at 8 weeks; if symptoms return, start maintenance therapy

Maintenance treatment:
* 1st line: PPI at the lowest dose

  • Alternative: H2RA, if there is no erosive esophagitis and it relieves symptoms
  • Not recommended: metoclopramide or sucralfate

Weight loss has the best evidence for improvement of symptoms

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6
Q

How do antacids work?

A
  • They neutralize gastric acid (producing salt and water), which increases gastric pH
  • They provide relief within minutes as they are not systemically absorbed but the duration of relief is short (30-60 minutes)
  • Suitable for mild and infrequent symptoms
  • Patients using antacids containing aspirin (e.g., Alka-Seltzer) should be made aware of the serious bleeding risk if used too frequently
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7
Q

Antacids - brand/generic

A

Calcium carbonate (Tums)
* + magnesium (Mylanta Supreme)
* + simethicone (anti-gas) (Maalox Advanced Maximum Strenght)

Magnesium hydroxide (Milk of Magnesia)
* + aluminum (Gaviscon, Mag-Al)
* + aluminum + simethicone (Mylanta classic)

Sodium bicarbonate/aspirin/citric acid (Alka-Seltzer)

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8
Q

Antacids - warnings, SEs, dosing

A

Dosing:
* 4 - 6 times/day

Warnings:
* Aluminum and magnesium can accumulate with severe renal dysfunction

Side Effects:
* Calcium: constipation
* Aluminum: constipation
* Magnesium: loose stools

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9
Q

T/F: Calcium-containing antacids may be preferred in pregnancy

A
  • True
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10
Q

How do H2RAs work?

A
  • They reversibly inhibit H2 receptors on gastric parietal cells, which decreases gastric acid secretion
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11
Q

H2RAs - brand/generic and dosing

A

Famotidine (Pepcid AC)
* OTC: 10-20 mg 1-2 times daily PRN

  • Rx: 20 mg BID (also in injection form)

Ranitidine (Zantac, Ranitidine Acid Reducer)
* OTC: 75-150 mg 1-2 times daily PRN

  • Rx: 150 mg BID (also in injection form)

Cimetidine (Tagamet HB)
* OTC: 200 mg 1-2 times daily PRN

  • Rx: 400 mg Q6H

All Ranitidine products were removed from the market in April 2020

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12
Q

H2RAs - Warnings, SEs

A

Warnings:
* Confusion, usually reversible (risk factors: elderly, severely ill, renal impairment)

  • Decrease dose when CrCl <50 mL/min (famotidine, ranitidine, nizatidine) or CrCl <30 mL/min (cimetidine)
  • Avoid cimetidine due to DIs and SEs
  • Use caution with CHS depressants (especially in elderly) due to risk of additive delirium, dementia and cognitive impairment

Side Effects:
* Cimetidine (high doses): gynecomastia, impotence

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13
Q

How do PPIs work?

A
  • They irreversibly bind to the gastric H+/K+ -ATPase pump (the proton pump) in parietal cells which blocks gastric acid secretion
  • PPIs are the most effective medications for GERD, an 8 week course of treatment is recommended for relief and heal erosions
  • If used long-term as maintenance treatment, the lowest effective dose should be used
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14
Q

PPIs - brand/generic, directions to take

A

Esomeprazole (Nexium)
* Take at least 60 minutes before breakfast

Lansoprazole (Prevacid, Prevacid SoluTab)
* Take before breakfast

Omeprazole (Prilosec)
* Take before breakfast

Dexlansoprazole (Dexilant)
* Take without regard to meals

Pantoprazole (Protonix)
* Tablet: take without regard to meals
* Oral suspension: take 30 minutes before a meal

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15
Q

PPIs - dosing

A

Dexlansoprazole (Dexilant)
* Rx: 30-60 mg daily

Esomeprazole (Nexium, Nexium 24HR, Nexium I.V.)
* OTC: 20 mg daily

  • Rx: 20-4- mg daily
    + naproxen (Vimovo)

Lansoprazole (Prevacid, Prevacid SoluTab, Prevacid 24HR)
* OTC: 15 mg daily

  • Rx: 15-30 mg daily

Omeprazole (Prilosec, Prilosec OTC)
* OTC: 20 mg daily

  • Rx: 20-40 mg daily

Pantoprazole (Protonix)
* Rx: 40 mg daily

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16
Q

PPIs - Warnings

A

Warnings:
* C.difficile - associated diarrhea (CDAD)

  • Hypomagnesemia
  • Vitamin B12 deficiency with prolonged use (>=2 years)
  • Osteoporosis-related bone fractures with high-doses or long-term (>=1 year) use
  • May diminish the therapeutic effect of clopidogrel, do not use omeprazole and esomeprazole while taking clopidogrel
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17
Q

T/F: Pantoprazole and esomeprazole are the only PPIs available IV

A
  • True
18
Q

T/F: Dexlansoprazole, esomeprazole, lansoprazole, aomeprazole and rabeprazole capsules can be opened (not crushed), mixed in applesauce and swallowed immediately (without chewing)

A
  • True
19
Q

H2RA formulations

OTC, ODT, Oral solution/suspension, Injection

A

OTC:
* Cimetidine
* Famotidine
* Ranitidine

ODT:
* N/A

Oral solution/suspension:
* Cimetidine
* Famotidine
* Nizatidine
* Ranitidine

Injection:
* Famotidine
* Ranitidine

All Ranitidine products were removed from the market in April 2020

20
Q

PPI - formulations

A

OTC:
* Esomeprazole
* Lansoprazole
* Omeprazole

ODT:
* Lansoprazole
* Omeprazole

Oral solution/suspension:
* Lansoprazole

Packets for suspension:
* Esomeprazole
* Omeprazole
* Pantoprazole

Injection:
* Esomeprazole
* Pantoprazole

All Ranitidine products were removed from the market in April 2020

21
Q

What are the risks associated with PPI therapy?

A
  • Long-term use of PPIs causes chronic changes in gastric pH, which can increase the risk of GI infections, including C.difficile and possibly pneumonia
  • PPIs increase the risk of osteoporosis and fractures
  • Beers Criteria: PPIs not be used beyond 8 weeks in elderly patients unless there is a clear indication
22
Q

How does Metoclopramide work in GERD?

A
  • Most commonly used when patients have coexisting gastroparesis
  • It is a dopamine antagonist, causing accelerated gastric emptying and increased LES tone
23
Q

Metoclopramide - brand/generic, dosing, BWs, warnings, SEs

A

Metoclopramide (Reglan) dosing:
* 10-15 mg QID 30 min before meals and bedtime

  • CrCl <60 mL/min: decrease dose 50% (to avoid CNS/EPS side effects)

Boxed Warning:
* Tardive dyskinesia

Warnings:
* EPS (including acute dystonia)

  • Parkinsonian-like symptoms
  • Avoid use in patients with Parkinson disease
  • Do not use in combination with antipsychotic drugs - droperidol and promethazine
  • Monitor for serotonin syndrome when used in combination with SSRIs, SNRIs or TCAs

Side Effects:
* Drowsiness

24
Q

Drugs with decreased absorption when taken with PPIs, H2RAs and antacids

A

Antiretrovirals
* rilpivirine (NNRTI), atazanavir (PI)

Antivirals
* ledipasvir, velpatasvir/sofosbuvir

Azole antifungals
* itraconazole, ketoconazole
* posaconazole oral suspension (absorption decreased by PPIs and and H2RAs only)

Cephalosporins (oral)
* cefpodoxime, cefuroxime

Iron products

Mesalamine

Risedronate DR

Tyrosine kinase inhibitors
* dasatanib, erlotinib, pazopanib

These medications require an acidic gut

25
Q

Oral drugs/drug classes that antacids bind and cause decrease in absorption

A

Antiretrovirals (INSTIs):
* bictegravir, dolutegravir, elvitegravir, raltegravir

Bisphosphonates
Isoniazid
Levothyroxine
Mycophenolate
Quinolones
Sotalol
Steroids (especially budesonide)
Tetracyclines

Due to the short duration of action of antacids, this type of interaction can often be alleviated by separating administration of the interacting drugs

26
Q

H2RA - DIs

A
  • Cimetidine is an inhibitor of CYP450 enzymes (e.g., CYP2C19, CYP3A4 and CYP1A2)
  • Avoid use cimetidine with dofetilide
27
Q

PPIs - DIs

A
  • All PPIs inhibit CYP2C19
  • Omeprazole and esomeprazole can decrease the effectiveness of clopidogrel (a prodrug) through CYP2C19 inhibition. Do not use them together
28
Q

What are the causes of Peptic Ulcer Disease (PUD)?

A

H.pylori
* Positive ulcers
* A spiral-shaped, gram negative bacterium

NSAID-induced ulcers

Stress ulcers

29
Q
A
30
Q

What are symptoms and diagnosis of PUD?

A

Diagnosis:
* Endoscopy

Symptoms:
* Dyspepsia

  • Gastric pain in the middle or upper stomach
  • Heartburn, belching, bloating, cramping, nausea
  • Anorexia
  • If the ulcer duodenal (usually caused by H.pylori), pain is worse 2-3 hours after eating; eating food or taking antacids lessens pain
  • If its gastric ulcer (primarily from NSAIDs), eating generally worsens the pain
31
Q

What are diagnostic tests for H.pylori?

A
  • Urea breath test (UBT)
  • Fecal antigent test
  • PPIs, bismuth and antibiaotics should be dicontinued 2 weeks prior to these tests to avoid false negative results
32
Q

What is the first-line treatment for H.plori infection?

A
  • Quadruple therapy is the first-line therapy for H.pylori due to failure rates with triple therapy
  • Triple therapy is only recommended as first-line if clarithromycin resistance rates are low (<15%)
  • Do not make drug substitutions in H.pylori eradication regimen
33
Q

Bismuth Quadruple Therapy

A

First-line, especially if;
* Local resistance rates to clarithromycin are high (>=15%)

  • The patient has had a previous macrolide exposure
  • Patient has penicillin allergy
  • Triple therapy failed

Drug regimen: Take for 10-14 days

1) Bismuth subsalicylate 300 mg QID + Metronidazole 250-500 mg QID + Tetracycline 500 mg QID + PPI BID

     OR

2) 3-in-1 combination product + PPI:
* Pylera (bismuth subcitrate potassium 420 mg + metronidazole 375 mg + tetracycline 375 mg) QID + PPI BID

Alcohol use:
* Do not use metronidazole

Pregnancy/Children:
* Do not use tetracycline

34
Q

Concomitant Therapy

A

Use only if;
* Local resistance rates to clarithromycin are low (<15%)

  • Patient has had no previous exposure to a macrolide
  • Preferred over clarithromycin triple therapy if previous macrolide exposure

Drug Regimen: Take for 10-14 days
* Amoxicillin 1,000 mg BID + Clarithromycin 500 mg BID + Metronidazole 250 - 500 mg QID + PPI BID

35
Q

Clarithromycin Triple Therapy

A

Use only if;
* Local resistance rates to clarithromycin are low

  • Patient has had no previous exposure to a macrolide

Dosing Regimen: Take for 10-14 days

1) Amoxicillin 1,000 mg BID + Clarithromycin 500 mg BID + PPI BID (or esomeprazole 40 mg daily)

 OR

2) 3-in-1 combination product + PPI:
* Prevpac (amoxicillin + clarithromycin + lansoprazole)

Penicillin allergy: replace amoxicillin with metronidazole 500 mg TID

36
Q

What causes NSAID-induced ulcers?

A
  • The chronic use of NSAIDs increases the risk of gastric (GI) ulcers
37
Q

NSAIDs should be used with caution in any person with __ or __ disease

Fill in the blanks

A
  • Cardiovascular
  • Renal
38
Q

T/F: NSAIDs with selective inhibition of COX-2 (e.g., celecoxib) have decreased GI risk but increased CV risk compared to non-selective NSAIDs

A
  • True
39
Q

List NSAIDs that approach selectivity of celecoxib

A
  • Meloxicam
  • Nabumetone
  • Diclofenac
  • Etodolac
40
Q

Name combination products marketed to reduce the risk of NSAID-induced ulcers

A

Naproxen/esomeprazole (Vimovo):
* Indicated to relieve osteoarthritis and rheumatoid arthritis

Aspirin/omeprazole (Yosprala):
* Secondary prevention of cardiovascular and cerebrovascular events in patients at risk for aspirin-associated ulcers

41
Q

What are the risk factors for NSAID-induced ulcers?

A
  • Age > 60 years
  • History of PUD (including H.pylori-induced)
  • High-dose NSAIDs
  • Using > 1 NSAID (e.g., ibuprofen plus aspirin)
  • Concomitant use of anticoagulants, steroids, SSRIs or SNRIs
42
Q

What are cytoprotective drugs and their important drug effects?

A

Misoprostol (Cytotec) + diclofenac 50 mg (Arthrotec):
* A protaglandin E1 analog that replaces the gastro-protective prostaglandins removed by NSAIDs

  • BW: abortifacient
  • Arthrotec: NSAIDs increase the risk of serious GI events and CV disease
  • SEs: diarrhea, abdominal pain

Sucralfate (Carafate):
* A sucrose-sulfate-aluminum complex and can interact with albumin and fibrinogen to form a physical barrier over an open ulcer

  • Take before meals
  • SEs: constipation
  • Difficult to use due to binding interactions (seperate antacids by 30 min and take other drugs 2 hours before or 4 hours after)