Selection of drugs to treat gastro-oesophageal reflux disease

The role of drug interactions

David A. Flockhart, Zeruesenay Desta, Subena K. Mahal

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Gastro-oesophageal reflux disease is probably the most common acid-peptic disease in Western countries, and the successful treatment of mild to moderate disease with pharmacotherapy has become commonplace. A large number of effective drugs are now available, and so the decision-making process for physicians increasingly relies on considerations other than pure efficacy. Cost, adverse effects and drug interactions have therefore become important, particularly in the most vulnerable patients - children, the elderly and patients who are ill and are taking medications that may influence the efficacy of antireflux therapy. Important drug interactions with antacids include the prevention of the absorption of antibacterials such as tetracycline, azithromycin and quinolones. H2 antagonists, proton pump inhibitors and prokinetic agents undergo metabolism by the cytochrome P450 (CYP) system present in the liver and gastrointestinal tract. Cimetidine is an inhibitor of CYP3A and it may cause significant interactions with drugs of narrow therapeutic range and low bioavailability that are metabolised by these enzymes. The gastroparietal proton pump inhibitors lansoprazole, omeprazole and pantoprazole are all primarily metabolised by a genetically polymorphic enzyme, CYP2C19, that is absent from approximately 3% of Caucasians and 20% of Asians. These drugs may also interact with CYP3A, but to a lesser extent. Interactions with prokinetic agents carry the greatest potential for harm. Metoclopramide is a dopamine antagonist that may cause extrapyramidal effects when administered alone at high concentrations, or when coadministered with anti-psychotic agents such as haloperidol or phenothiazines. Cisapride is clearly able to prolong the electrocardiographic QT interval and cause lethal ventricular arrhythmias when its metabolism is slowed by interaction with inhibitors of CYP3A, such as erythromycin, ketoconazole or itraconazole.

Original languageEnglish (US)
Pages (from-to)295-309
Number of pages15
JournalClinical Pharmacokinetics
Volume39
Issue number4
StatePublished - 2000
Externally publishedYes

Fingerprint

Esophageal Diseases
Gastroesophageal Reflux
Drug Interactions
Proton Pump Inhibitors
Pharmaceutical Preparations
Cisapride
Lansoprazole
Phenothiazines
Cytochrome P-450 CYP3A
Antacids
Azithromycin
Metoclopramide
Ketoconazole
Itraconazole
Omeprazole
Dopamine Antagonists
Cimetidine
Quinolones
Haloperidol
Erythromycin

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Selection of drugs to treat gastro-oesophageal reflux disease : The role of drug interactions. / Flockhart, David A.; Desta, Zeruesenay; Mahal, Subena K.

In: Clinical Pharmacokinetics, Vol. 39, No. 4, 2000, p. 295-309.

Research output: Contribution to journalArticle

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