General Pharmacology

Proton-Pump Inhibitors Pharmacology!

Oct 26th, 2020
proton-pump inhibitors pharmacology

Proton-Pump Inhibitors Pharmacology

Proton-pump inhibitors remain some of the most widely prescribed medicines. Here, in this review, we take a closer look at this effective drug class – examining indications, mechanism of action, side effects, and clinical pharmacology.

Proton-pump inhibitors are used in the treatment of conditions caused by excess gastric acid production. For example – they are used in the treatment of peptic ulcer disease, NSAID-associated ulcers, GERD, and the eradication of H. pylori infection. PPIs work through the irreversible inhibition of the proton pump – a pump found on gastric parietal cells.

PPIs can be identified through the suffix –prazole.

Examples of common proton-pump inhibitors include:

  • Omeprazole
  • Esomeprazole
  • Lansoprazole
  • Pantoprazole
  • Rabeprazole

PPIs are used in the treatment of the following conditions:

  • Peptic ulcer disease
  • NSAID-associated ulcers
  • Dyspepsia
  • Gastroesophageal reflux disease (GERD)
  • Barrett’s esophagus
  • Elimination of Helicobacter pylori infection

In the case of H. pylori infection, proton-pump inhibitors are used as part of “triple therapy”. Later in this review, we will discuss triple therapy in more detail.

For now, however, let’s take a moment to learn more about the mechanism behind proton-pump inhibitors pharmacology.

Mechanism of action

Proton-pump inhibitors reduce stomach acid production through irreversible inhibition of the proton pump – the H+/K+-ATPase, a pump present in gastric parietal cells. In this way, proton-pump inhibitors differ from H2 receptor antagonists (for example – ranitidine).

That’s because proton-pump inhibitors bind to the terminal phase of stomach acid production, whereas H2 receptor antagonists do not. This makes proton-pump inhibitors far more effective at reducing gastric acid production. And given their irreversible inhibition, PPIs offer more complete acid suppression.

Side effects

Notably, the mechanism of PPIs comes with metabolic consequences.

For example – stomach acid is necessary for digestion of nutrients – such as vitamin B12, proteins and calcium. When stomach acid production falls too low, this leads to a state known as achlorhydria.

However, PPIs – as a class – are very well tolerated.

Common side effects include:

  • Headache
  • Abdominal pain
  • Nausea
  • Fatigue
  • Dizziness
  • Hypomagnesemia

PPIs can mask symptoms of gastric cancer. Patients should be monitored for alarm symptoms, such as difficulty swallowing and weight loss.

There is tentative evidence that, when PPIs are administered to the elderly for prolonged periods, that it increases the risk of fractures.

Clinical Pharmacology

When we talk about the clinical pharmacology of PPIs, we must consider the following factors:

  • That for H. pylori infections, PPIs are combined with other medicines. It’s not uncommon for patients to take a PPI alongside two antibacterial drugs – such as clarithromycin (a macrolide) and amoxicillin (a penicillin). In the case of penicillin allergies, patients may be given metronidazole instead. This is known as “triple therapy”.
  • Given that PPIs can mask the presence of gastric cancer – patients should report alarm symptoms such as weight loss and difficulty swallowing.
  • That when PPIs are administered over the long-term, they increase the risk of hypomagnesemia – symptoms of which include tremors, seizures and cardiac arrhythmias. Patients may be switched to a H2 receptor antagonist.
  • Omeprazole interacts with clopidogrel, an antiplatelet drug. It decreases the activation of clopidogrel. By reducing the antiplatelet effect of clopidogrel, omeprazole may increase the risk of stroke and heart attack.
  • That by increasing gastric pH, PPIs increase the risk of Clostridium difficile infection. Hydrochloric acid is often necessary to destroy harmful microorganisms that enter the gastric orbit. PPIs also increase the risk of other bacterial infections such as peritonitis – particularly if the patient has co-morbid conditions, such as irritable bowel syndrome.
  • That PPIs are classified as pregnancy category C – meaning that “risk is not ruled out”.
  • That PPIs are typically administered in the morning, one hour before food. It typically takes several days before a definite therapeutic effect takes hold.

Proton-pump inhibitors have been around since the 1980s – the first PPI, omeprazole, being released in 1988.

Since then, PPIs have consistently remained a highly effective choice at reducing gastric acid production. As they inhibit the terminal phase in stomach acid production and because they remain very well tolerated, PPIs will continue to remain an important drug class in the clinician’s toolkit.

That concludes our review of proton-pump inhibitors pharmacology. Check back to our pharmacy blog soon for even more of the top pharmacology facts about medicines you need to know!