Proton pump inhibitor
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# Overview
Proton pump inhibitors (or "PPI"s) are a group of drugs whose main action is pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar effects, but different mode-of-action, called H2-receptor antagonists.  These drugs are among the most widely-selling drugs in the world as a result of their outstanding efficacy and safety. Structurally, the vast majority of these drugs are benzimidazole derivatives; however, promising new research indicates that imidazopyridine derivatives may be a more effective means of treatment.

# Clinical use
These drugs are utilized in the treatment of many conditions such as:
- dyspepsia
- peptic ulcer disease (PUD)
- Zollinger-Ellison syndrome
- gastroesophageal reflux disease (GORD/GERD)
- Barrett's esophagus
- prevention of stress gastritis
- gastrinomas and other conditions that cause hypersecretion of acid
- Laryngopharyngeal Reflux Disease
Despite their widespread use for these conditions, proton pump inhibitors' effectiveness has not been demonstrated in every case. For example, proton pump inhibitors do not change the length of Barrett's esophagus.

# Mechanism of action
Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase, or more commonly just gastric proton pump) of the gastric parietal cell. The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.
Targeting the terminal-step in acid production, as well as the irreversible nature of the inhibition, result in a class of drugs that are significantly more effective than H2 antagonists and reduce gastric acid secretion by up to 99%.
The lack of the acid in the stomach will aid in the healing of duodenal ulcers, and reduces the pain from indigestion and heartburn, which can be exacerbated by stomach acid. However, lack of stomach acid may also contribute to hypochlorhydria, a lack of sufficient hydrochloric acid, or HCl. Hydrochloric acid is required for absorption of nutrients, particularly calcium.
The proton pump inhibitors are given in an inactive form.  The inactive form is neutrally charged (lipophilic) and readily crosses cell membranes into intracellular compartments (like the parietal cell canaliculus) that have acidic environments.  In an acid environment, the inactive drug is protonated and rearranges into its active form.  As described above, the active form will covalently and irreversibly bind to the gastric proton pump, deactivating it.

# Pharmacokinetics
Generally, the absorption of proton pump inhibitors is unaffected by co-administration with food. The rate of omeprazole absorption, however, is decreased by concomitant food intake. Additionally, the absorption of lansoprazole and esomeprazole is decreased and delayed by food. These pharmacokinetic effects, however, reportedly have no significant impact on efficacy.
The elimination half-life of proton pump inhibitors ranges from 0.52 hours, however the effect of a single dose on acid secretion usually persists up to 23 days. This is because of accumulation of the drug in parietal cell canaliculi and the irreversible nature of proton pump inhibition.

# Examples of proton pump inhibitors
Clinically used proton pump inhibitors:
- Omeprazole (brand names: Losec, Prilosec, Zegerid)
- Lansoprazole (brand names: Prevacid, Zoton, Inhibitol)
- Esomeprazole (brand names: Nexium)
- Pantoprazole (brand names: Protonix, Somac, Pantoloc, Pantozol, Zurcal)
- Rabeprazole (brand names: Rabecid, Aciphex, Pariet)
There are currently three PPIs which have an IV formulation.  These include Protonix, Nexium, Pantozol and Zurcal.

# Adverse effects
Proton pump inhibitors are generally well tolerated, and the incidence of short-term adverse effects is relatively uncommon. The range and occurrence of adverse effects are similar for all of the proton pump inhibitors, though they have been reported more frequently with omeprazole. This may be due to its longer availability and hence clinical experience.
Common adverse effects include: headache, nausea, diarrhea, abdominal pain, fatigue, dizziness.
Infrequent adverse effects include: rash, itch, flatulence, constipation. Decreased cyanocobalamin (vitamin B12) absorption may occur with long-term use. Rarely PPI cause idiosyncratic reactions such as erythema multiforme, pancreatitis, Stevens Johnson syndrome and acute interstitial nephritis. 
It has been observed that gastric acid suppression, using H2-receptor antagonists and proton pump inhibitors, is associated with an increased risk of community-acquired pneumonia. It is suspected that acid suppression results in insufficient elimination of pathogenic organisms. It has therefore been suggested that patients at higher risk of pneumonia should only be prescribed proton pump inhibitors at lower doses and only when necessary. 
PPIs have also been shown to raise risk of C. dif infection.
Long-term use of proton pump inhibitors has been less studied. But in a study of 135,000 people 50 or older, those taking high doses of PPIs for longer than one year have been found to be 2.6 times more likely to break a hip.  Those taking smaller doses for 1 to 4 years were 1.2 to 1.6 times more likely to break a hip.  The risk of a fracture increased with the length of time taking PPIs.  Theories as to the cause of the increase are the possibility that the reduction of stomach acid reduces the amount of calcium dissolved in the stomach or that PPIs may interfere with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts.

# Discontinuation
Many patients (14% to 64%) who take chronic PPIs without clear indication, can have their PPI successfully discontinued according to a systematic review.