Proton pump inhibitors (PPIs) are substituted 2-pyridyl methyl sulfinyl benzimidazoles that inhibit the final common pathway in gastric acid secretion in the apical membrane of parietal cells regardless of the stimulus for acid secretion. As PPIs are inactivated in acidic media, they need to be protected from gastric acid by either enteric coated microspheres (mouth dissolving tablets) or capsules. For the best action, PPIs should be taken 30 minutes before breakfast as they best act on activated parietal cells which are activated after meal. Inhibition of acid secretion occurs after 1 hour and reaches maximum after 2 hours of administration. With daily administration it takes 2 to 8 days to have maximum effect and effect lasts for 3 to 5 days after stoppage of PPI. As PPIs takes 2 to 8 days for maximum effects, there is no role of PPIs as an immediate relief therapy.
Children (<10 years) often require higher per kilogram doses (2-2.5mg/kg/day for omeprazole and 1.4 mg/kg/day for lansoprazole) due to higher rates of metabolism as compared to adult and adolescent to obtained similar degree of acid suppression.
There is no significant difference in efficacy of one PPI over other.
Advantage of PPIs:
- More effective in relieving symptoms and healing esophagitis than any other acid suppressants
- Prolonged action (requires once daily dose)
- No tachyphylaxis on prolonged use
- Relatively safe drug on long term use.
Side effects of PPIs
In general PPIs are well tolerated with low side effects. The most frequently reported adverse effects are GI upsets(diarrhea/constipation), nausea, headache, dizziness and rash. Other rare side effects are community acquired pneumonia, interstitial nephritis on prolonged use.