Products
Proton pump inhibitors (PPIs) are commercially available in many countries in the form of film-coated tablets, MUPS tablets, capsules, as granules for preparation of an oral suspension, and as injectable and infusion preparations. The first active ingredient from this group to be approved in many countries was omeprazole (Antra, Losec), developed by Astra in the 1970s, in 1988, and in the USA in 1989 (Prilosec). Today, generics are available, and pantoprazole, omeprazole, and esomeprazole are also available without a physician’s prescription.
Structure and properties
Typical structural elements of proton pump inhibitors are the benzimidazole, sulfoxide (S=O), and pyridine. Protonation of the pyridine nitrogen results in accumulation in the acidic environment of the secretory tubules (canaliculi) of the vestibular cells. The sulfoxide is activated by a rearrangement to sulfenamide and binds to cysteines of the proton pump, which inactivates it in this way. The active ingredients are present as racemates. The pure enantiomers esomeprazole as well as dexlansoprazole are also marketed. PPIs are sensitive to acid and therefore must be administered in enteric-coated dosage forms.
Effects
Proton pump inhibitors (ATC A02BC) have antisecretory properties. They reduce gastric acid secretion by inhibiting the proton pump (H+/K+-ATPase) in the gastric vestibular cells irreversibly. They do not act locally from within the stomach, but are first absorbed in the intestine and travel through the bloodstream to the occupant cells. PPIs are prodrugs and are not converted from acid to their active form until they reach the canaliculi of the vestibular cells, where they bind covalently to the proton pump, inhibiting it. The inhibition of gastric acid secretion is dose-dependent and the full effect is delayed within a few days. The active ingredients have a short half-life but a long duration of action because of covalent binding, so once-daily dosing is usually sufficient.
Indications
Indications for use include:
- Gastric and intestinal ulcers
- Stomach burning, gastroesophageal reflux disease, dyspepsia.
- Reflux esophagitis
- Gastritis
- Helicobacter pylori eradication (combination therapy with antibiotics).
- As “gastric protection” during treatment with non-steroidal anti-inflammatory drugs.
- Zollinger-Ellison syndrome
Dosage
According to the professional information. It is recommended to take the drugs half an hour to an hour before meals. The maximum effect is achieved within a few days. Once daily administration is usually sufficient. For some indications, twice-daily administration may be necessary.
Active ingredients
- Esomeprazole (Nexium, generic).
- Lansoprazole (Agopton, generic).
- Dexlansoprazole (Dexilant, generic).
- Omeprazole (Antramumps, generics).
- Pantoprazole (Pantozol, generics).
- Rabeprazole (Pariet, generics)
Ilaprazole (Noltec) is not commercially available in many countries.
Contraindications
The drugs are contraindicated in hypersensitivity. For complete precautions, see the drug label.
Interactions
Proton pump inhibitors are metabolized by CYP450 isozymes, particularly CYP3A and CYP2C19. Appropriate drug-drug interactions must be considered. The antiplatelet agent clopidogrel (Plavix, generics) is biotransformed to the active metabolite by CYP2C19. PPIs that inhibit CYP2C19 may reduce the efficacy of clopidogrel. Raising gastric pH may adversely affect the absorption of other drugs and nutrients (eg, vitamin B12).
Adverse effects
The most common potential adverse effects include headache, dizziness, and digestive symptoms such as nausea and diarrhea. Proton pump inhibitors may cause magnesium deficiency (hypomagnesemia). Blood levels should be monitored during long-term therapy.
