Problems Associated with Deprescribing of Proton Pump Inhibitors

Abstract

Proton pump inhibitors (PPIs) are recommended as a first-line treatment for gastroesophageal reflux disease (GERD) and other acid related disorders. In recent years, concerns have been raised about the increasing prevalence of patients on long-term PPI therapy and inappropriate PPI use. It is well known that short-term PPI therapy is generally well tolerated and safe; however, their extensive long-term use is a major global issue. One of these long-standing concerns is PPI-induced gastrin elevation secondary to hypoacidity. Hypergastrinemia is believed to play a role in rebound hyperacidity when PPIs are discontinued resulting in induced dyspeptic symptoms that might result in the reinstitution of therapy. Gastrin exerts tropic effects in the stomach, especially on enterochromaffin-like (ECL) cells, and concerns have also been raised regarding the potential progression to dysplasia or tumor formation following long-term therapy. It is well known that a substantial number of patients on long-term PPI therapy can discontinue PPIs without recurrence of symptoms in deprescribing trials. What is unknown is how sustainable deprescribing should be undertaken in practice and how effective it is in terms of reducing long-term outcomes like adverse drug events, morbidity and mortality. Moreover, there is no clear consensus on when and how deprescribing strategies should be attempted in practice. This review sought to summarize the harms and benefits of long-term PPI therapy with special focus on gastrin elevation and its relation to deprescribing studies and future interventions that may improve PPI use.

Gastrointestinal sequelae 90 days after discharge for COVID-19

“…PPIs were often used for aspiration prophylaxis in patients admitted for suspected COVID-19 receiving anaesthesia, parenteral nutrition, or other acid-related treatments. Acid rebound is a known consequence of deprescribing PPIs, 7 so it might be expected that PPI treatment during hospitalisation was associated with acid reflux after discharge.…”

Problematiske protonpumpehemmere

“…Danske og islandske reseptregisterstudier viser at antallet nye brukere av protonpumpehemmere er konstant, mens det totale antallet brukere øker tilsvarende som i Norge. Dette kan indikere at vanskeligheter med seponering, heller enn økt behov for protonpumpehemmere i befolkningen, ligger til grunn for det økte forbruket (3). Etter vår mening skyldes det høye forbruket i Norge for en stor del forskrivning til pasienter som ikke burde brukt protonpumpehemmere.…”

“…Seponeringsstudier viser at mange pasienter ikke klarer å trappe ned bruk av protonpumpehemmere, og at støtte og motivering fra lege er viktig (3). Vi anbefaler at pasientene informeres om at tilbakefall av de syrerelaterte problemene er sannsynlig, og at sure oppstøt av og til er et normalfenomen knyttet til enkelte typer mat og andre livsstilsfaktorer.…”

Deprescribing and Optimal Selection of Proton Pump Inhibitors (Contributions of the 26th United Russian Gastroenterology Week)

“…наук Т. Л. Лапиной содержал критическую оценку соотношения «польза-риск» в случаях применения ИПП при лече нии кислотозависимых заболеваний. Как было показано, все нежелательные эффекты применения ИПП можно разделить на 2 группы: связанные с кислотосупрессивным эффектом (например, гипохлоргидрия с последующим повышением риска кишечных инфекций, гипергастринемия с повышением плотности энтерохромаффиноподобных клеток (ECL) в слизистой оболочке желудка) и не связанные с ним (идиосинкразия) [29,30]. К последней группе относятся также нежелательные явления, обусловленные фармакокинетическим взаимодействием с лекарственными препаратами, метаболизирующимися системой цитохрома Р450 (СYP450).…”

“…Повышение уровня интрагастрального рН в результате применения ИПП имеет обязательным последствием возникновение гипергастринемии, что может привести к гиперплазии энтерохромаффиноподобных клеток (ECL-клеток) [29,30]. Контролируемые исследования не подтвердили высказывавшиеся опасения о возможности возникновения при длительном приеме ИПП полипов и рака желудка, а также карциноида.…”