GERD: BCPS 2013 Review

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GI Notes Just For You! GERD

  1.  Lifestyle modification
  2. Antacids
  3. Acid suppression (prn/scheduled)
    1.  PPI
    2. H2RA
    3.  Promotility agents

 

AGA Guideline Recommendations

  • Empiric drug therapy is appropriate for patients with uncomplicated heartburn
  • Use of antisecretory drugs for pts with esophageal GERD symptoms (with or without esophagitis) is strongly recommended (grade A).
  • Data are weak to support using PPIs or H2RAs above standard doses.  However, BID dosing of PPIs is appropriate in patients who continue to have symptoms on once-daily PPI therapy (grade B)
  • Antacids are the fastest acting drugs and should be used for those patients that wants to take medications for symptoms.  Safe to take with H2RA or PPIs.
  • On-demand therapy is not recommended for erosive esophagitis.
  • No evidence of improved efficacy by adding a bedtime dose of H2RA to twice-daily PPI therapy
  • Data weak to support the use of PPIs in patients with extraesophageal symptoms

 

AGA Guildeline – Extraesophageal symptoms (chronic cough, laryngitis, and asthma)

  • The presence of extraesophageal symptoms in the absence of esophageal GERD is rare.
  • Evidence is fair for the use of once-or twice-daily PPI therapy in patients with an extraesophageal syndrome and a concomitant esophageal GERD syndrome (grade B).  A two month trail of twice-daily PPI therapy would be an appropriate therapy for these patients.
  • Evidence is for the use of once-or twice-daily PPI therapy in patients with an extraesophageal symdrome in the absence of an esophageal GERD syndrome (grade D).
  • Evidence is insufficient to recommend once-or twice-daily PPI therapy for patients with suspected reflux cough syndrome.

The Drugs

  1. ANTACIDS – calcium, aluminum, magnesium OTC.  Neutralizes acid and raises intragastric pH resulting in decreased activation of pepsinogen and increased LES pressure; rapid onsent of action but short duration, necessitating frequent dosing.  FIRST LINE for intermittent (< 2 times/week) symptoms or as breakthrough therapy for those on PPI/H2RA therapy; not appropriate for healing established esophageal erosions
    1.  Adverse effects

i.      Constipation (aluminum)

ii.      Diarrhea (magnesium)

iii.      Accumulation of aluminum/magnesium in renal disease with repeated dosing.

  1. Drug interactions

i.      Chelation (fluoroquinolones, tetracyclines),

ii.      Reduced absorption because of increases in pH (ketoconazole, itraconazole, iron, atazanavir, delavirdine, indinavir, nelfinavir)

iii.      Increases in absorption leading to potential toxicity (raltegravir, saquinavir)

 

  1.  HISTAMINE-2 RECEPTOR ANTAGNOSITS – Reversibly inhibit histamine-2 receptors on the parietal cell.  All available OTC.
    1. Adverse effects

i.      CNS effects like dizziness, h/a, fatigue, somnolence, and confusion mostly with elderly and compromised renal function.

ii.      Prolonged cimetidine – rare development of gynecomastia

  1.  Drug interactions

i.      Drugs dependent on lower pH for absorption:  ketoconazole, itraconazole, iron, atazanavir, delavirdine, indinavir, nelfinavir

ii.      Increases in absorption leading to potential toxicity:  raltegravir, squinavir

iii.      Cimetidine inhibits cytochrome P450 (CYP) enzymes 1A2, 2C9, 2D6, and 3A4 – Warfarin, theophylline, and other agents may be affected.  Cimetidine also competes for tubular secretion in the kidney.

 

 

  1.  PROTON PUMP INHIBITORS – Irreversibly inhibit the final step in gastric acid secretion
    1. Most effective before meals; for divided dosing, give evening dose before evening meal instead of at bedtime
    2. Adverse effects – h/a, dizziness, nausea, diarrhea, and constipation.  Long-term use is not associated with significant increases in endocrine neoplasia or symptomatic vitamin B12 deficiency.

i.      Cohort study – ELEVATED risk of CAP with these agents (H2RA and PPI) – immunocompromised, the elderly, children, and those with asthma or COPD

ii.      Prospective cohort study – increased risk of HAP in nonventilated patients who were prescribed PPIs

iii.      Increased risk of fractures – not recommend bone density screening or calcium supplementation.

iv.      C diff infection – increased risk

v.      Hypomagnesiumia

  1.  Drug interactions

i.      Inhibition of CYP45 – inhibits the metabolism of substrates such as diazepam through CYP2C19 inhibition

ii.      Reduced effect of clopidogrel (CYP2C19) – omeprazole most implicated

iii.      High dose IV MTX – higher risk of MTX toxicity.  Either switch to ranitidine or hold PPI dose for 2 days before and after MTX admin may help

iv.      pH-dependent absorption (ketoconazole, itraconazole, protease inhibitors)

 

  1.  PROMOTILITY AGENTS – guidelines recommend against the use of metoclopramide as adjunctive therapy or monotherapy in patients with both esophageal and extraesophageal symptoms because the risk of adverse effects (EPS/tardive dyskinesia) outweighs the benefit (grade E).  Metoclopramide has a black box warning for Tardive Dyskinesia.
    1. Works through cholinergic mechanisms to facilitate increased gastric emptying.

i.      Metoclopramide – dopamine antagonist; needs to be dosed several times a day; associated with dizziness, fatigue, somnolence, drowsiness, EPS, and hyperprolactinemia.  New 5- and 10-mg ODT formulations.  Indicated for GERD and diabetic gastroparesis

ii.      Bethanechol – Cholinergic agonist; poorly tolerated because of adverse effects such as diarrhea, blurred vision, and abd cramping; may also increase gastric acid production

iii.      Cisapride – Restricted.  Removed from market for torsades when used in combination w/drugs inhibiting CYP3A4.