Proton Pump Inhibitors

PPIs reduce gastric acid production by inhibiting the gastric parietal cell proton pump (H+/K+ ATPase).

PPIs are currently indicated for GORD, reflux oesophagitis, duodenal and benign gastric ulcers, treatment and prophylaxis of NSAID-induced ulceration, and with antibiotics for eradication of H. pylori in peptic ulcers. They can also be used for the prophylaxis of acid aspiration during general anaesthesia.

Although not effective in all patients, PPIs are currently considered as the standard therapy for moderate to severe EOR.

Efficacy of PPIs in EOR

  • Noordzij performed a placebo-controlled, double-blind cross-over study in patients with proven reflux laryngitis and showed that symptoms of hoarseness and throat-clearing improved significantly with omeprazole (40 mg twice daily). However, a significant placebo effect was also observed for most symptoms.[Noordzij JP, 2001]
  • Wo showed that high-dose omeprazole (40 mg at night) given for 8 weeks is a reasonable, initial approach for patients with gastro-oesophageal-related posterior laryngitis. 67% of patients responded fully to therapy and a significant number of patients do well with a short course of therapy.[Wo JM, 1997] However, one third of patients did not respond to the therapy.
  • Cough and reflux symptoms continued to improve even after discontinuation of 8 weeks of treatment with omeprazole 40 mg once daily.[Kiljander TO, 2000]
  • After 8 weeks of omeprazole 40 mg once daily treatment, there was a reduction in nocturnal asthma symptoms, whereas daytime asthma outcome did not improve.[Kiljander TO, 1999]
  • Benini demonstrated that patients with reflux oesophagitis treated with omeprazole for 5 days had an improved cough threshold, as well as improved respiratory and gastro-oesophageal symptoms.[Benini L, 2000]
  • Eubanks demonstrated that twice-daily PPI therapy improves clinical symptoms and decreases pharyngeal reflux episodes in patients with GORD-associated respiratory complications.[Eubanks TR, 2001]
  • The combination therapy of twice-daily pantoprazole 40 mg and cisapride 20 mg was effective in relieving symptoms and improving endoscopic findings in the majority of patients studied.[Hamdan AL, 2001]

Maintenance therapy with PPIs

If symptoms recur after stopping treatment or if continued low doses are required to control symptoms, then some patients will require PPI treatment long-term.

Long-term safety of omeprazole has been demonstrated, with no complications reported in 11 years of maintenance therapy.[Klinkenberg-Knol EC, 2000]

However, treatment with PPIs can be followed by rebound acid hypersecretion. Some recommend that PPIs should not be used long term in younger patients (under 50 years) due to profound inhibition of gastric acid and associated hypergastrinaemia, which may lead to the development of gastric carcinomas.[Waldum HL, 2000]

Maintenance treatment with high-dose PPIs can also be costly.

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