Treatment of Patients with Persistent Symptoms on Once Daily PPI

Because acid-suppressive therapy is very effective and has few side effects, specialists (gastroenterologists and GI surgeons) are likely to see only the "tip of the iceberg" represented by patients with severe or persistent symptoms not responsive to standard treatment (Bennet and Castell, 1999).

The concept of treatment failure of daily PPI was initially surprising because early literature obtained from parietal cell cultures described these drugs as irreversibly binding to the proton pumps, the hydrogen/potassium ATPases that functions as the final common step in acid secretion. The isolated cell studies showed 1,000-fold accumulation of these drugs in the canaliculi, relating the area under the plasma concentration curve and net plasma concentration to their effect, and indicated that synthesis of proton pumps takes 36 to 96 hours. In contrast, 24-hour intragastric pH studies in healthy volunteers and GERD patients showed that the mean duration of intragastric pH > 4 following a steady state single dose of any of the five PPIs ranges from 10 to 14 hours. This can be explained by a variety of factors, including that, in vivo PPIs bind 70 to 80% of active pumps, not all pumps are active at the same time, synthesis of new pumps is continuous, and the halflife of the PPIs range between 2 to 4 hours.

Several studies indicate that individual patient responses to PPIs vary widely. Therefore, we recommend switching to another PPI as the first step in patients not responding to one PPI. Attention should also be paid to the frequency and severity of symptoms. Patients with occasional breakthrough symptoms should be instructed to take an antacid as needed.

In patients with continuing symptoms, the next step is to increase the dose of the PPI. Divided doses of PPIs work better than simply doubling the morning dose. It is also important to pay attention to the timing of PPI dosing in relation to meals. The ideal window to take the PPI is 15 to 30 minutes before meals. This allows absorption of the medication to provide availability to the proton pumps when they are activated by the meal. PPIs taken before meals provide the best intragastric pH control (Khoury et al, 1999). Inadequate timing is frequently seen clinically, especially when patients are prescribed PPI twice daily without further instructions, as they frequently take the medication in the morning and before bedtime (without a meal). Table 9-2 outlines the "step-up" approach to acid suppression therapy we use for GERD. Going directly to PPI dosing before breakfast and dinner is another "step-up" approach.*

Constipation Prescription

Constipation Prescription

Did you ever think feeling angry and irritable could be a symptom of constipation? A horrible fullness and pressing sharp pains against the bladders can’t help but affect your mood. Sometimes you just want everyone to leave you alone and sleep to escape the pain. It is virtually impossible to be constipated and keep a sunny disposition. Follow the steps in this guide to alleviate constipation and lead a happier healthy life.

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