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 The group followed and has largely superseded another group of pharmaceuticals with similar effects, but different mode-of-action, called H₂-receptor antagonists.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, all of these drugs are substituted benzimidazoles. Oral medication A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... Gastric acid is, together with several enzymes and the intrinsic factor, one of the main secretions of the stomach. ... Pharmacology (in Greek: pharmacon (φάρμακον) meaning drug, and logos (λόγος) meaning science) is the study of how substances interact with living organisms to produce a change in function. ... An H2-receptor antagonist, often shortened to H2-antagonist, is a drug used to block the action of histamine on parietal cells in the stomach, decreasing acid production by these cells. ... Benzimidazole is a heterocyclic aromatic organic compound. ...

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)
• prevention of stress gastritis
• gastrinomas and other conditions that cause hypersecretion of acid

A benign gastric ulcer (from the antrum) of a gastrectomy specimen. ... Zollinger-Ellison syndrome is a disorder where increased levels of the hormone gastrin are produced, causing the stomach to produce excess hydrochloric acid. ... It has been suggested that heartburn be merged into this article or section. ... Gastritis is a medical term for inflammation of the lining of the stomach. ... In humans, gastrin is a hormone that stimulates secretion of gastric acid by the stomach. ...

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. A proton pump is an integral membrane protein that is capable of moving protons across the membrane of a cell, mitochondrion, or other subcellular compartment, thereby creating a difference or gradient in both pH and electrical charge (ignoring differences in buffer capacity) and tending to establish an electrochemical potential. ... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... General Name, Symbol, Number potassium, K, 19 Chemical series alkali metals Group, Period, Block 1, 4, s Appearance silvery white Atomic mass 39. ... ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and a free phosphate ion. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Gastric hydrogen potassium ATPase also know as H+/K+ ATPase // Function and location The gastric hygrogen potassium ATPase or H+/K+ ATPase is the proton pump of the stomach and as such is the enzyme primarily responsible for the acidification of the stomach contents. ... A proton pump is an integral membrane protein that is capable of moving protons across the membrane of a cell, mitochondrion, or other subcellular compartment, thereby creating a difference or gradient in both pH and electrical charge (ignoring differences in buffer capacity) and tending to establish an electrochemical potential. ... Parietal cells (also called oxyntic cells) are cells located in the stomach epithelium. ...

Targeting the terminal-step in acid production, as well as the irreversible nature of the inhibition, result in a class of drugs that is significantly more effective than H₂ antagonists and reduces gastric acid secretion by up to 99%. An H2-receptor antagonist, often shortened to H2-antagonist, is a drug used to block the action of histamine on parietal cells in the stomach, decreasing acid production by these cells. ...

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 caused by excess stomach acid. In anatomy of the digestive system, the duodenum is a hollow jointed tube connecting the stomach to the jejunum. ...

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. This article or section does not cite its references or sources. ... Image:CellWallDrawing. ... Covalent bonding is a form of chemical bonding characterized by the sharing of one or more pairs of electrons between atoms, in order to produce a mutual attraction, which holds the resultant molecule together. ...

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 (Wyeth Australia, 2004; AstraZeneca, 2005). Pharmacokinetics is a branch of pharmacology dedicated to the study of the time course of substances and their relationship with an organism or system. ...

The elimination half-life of proton pump inhibitors ranges from 0.5–2 hours, however the effect of a single dose on acid secretion usually persists up to 2–3 days. This is because of accumulation of the drug in parietal cell canaliculi and the irreversible nature of proton pump inhibition. The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ... Parietal cells (also called oxyntic cells) are cells located in the stomach epithelium. ...

Examples of proton pump inhibitors

The proton pump inhibitor Omeprazole.

Clinically used proton pump inhibitors: Image File history File links Omeprazole. ... Image File history File links Omeprazole. ...

• Omeprazole (brand names: Losec®, Prilosec®)
• Lansoprazole (brand names: Prevacid®, Zoton®, Inhibitol®)
• Esomeprazole (brand names: Nexium®)
• Pantoprazole (brand names: Protonix®, Somac®, Pantoloc®)
• Rabeprazole (brand names: Rabecid®, Aciphex®, Pariet®)

Omeprazole (INN) (IPA: ) is a proton pump inhibitor (brand names Antra® in Italy) used in the treatment of dyspepsia, peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD/GERD) and Zollinger-Ellison syndrome. ... Lansoprazole, marketed as Takepron (in Japan), Prevacid and Zoton, is a proton pump inhibitor which prevents the stomach from producing acid. ... Esomeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease (PUD), GERD and Zollinger-Ellison syndrome. ... Pantoprazole is a proton pump inhibitor drug used for short-term treatment of erosion and ulceration of the esophagus caused by gastroesophageal reflux disease. ... Rabeprazole is a proton pump inhibitor sold (as its sodium salt) under the brand name Aciphex and Pariet (distributed by Janssen-Ortho). ...

Adverse effects

Proton pump inhibitors are generally well tolerated, and the incidence of 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. Adverse effect, in medicine, is an abnormal, harmful, undesired and/or unintended side-effect, although not necessarily unexpected, which is obtained as the result of a therapy or other medical intervention, such as drug/chemotherapy, physical therapy, surgery, medical procedure, use of a medical device, etc. ...

Common adverse effects include: headache, nausea, diarrhoea, abdominal pain, fatigue, dizziness. (Rossi, 2004) A headache (medically known as cephalalgia, sometimes spelled as cephalgia) is a condition of pain in the head; sometimes neck or upper back pain may also be interpreted as a headache. ... For other uses, see Nausea (disambiguation). ... Diarrhoea is the correct way to spell the word Diarrhoea. ... Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. ... The word fatigue is used in everyday living to describe a range of afflictions, varying from a general state of lethargy to a specific work induced burning sensation within muscle. ... Dizziness (Latin: Vertigo) is the sensation of instability. ...

Infrequent adverse effects include: rash, itch, flatulence, constipation. Decreased cyanocobalamin (vitamin B12) absorption may occur with long-term use (Rossi, 2006). A typical rash A rash is a change in the skin which affects its appearance or texture. ... An itch (Latin: pruritus) is a sensation felt on an area of skin that makes a person or animal want to scratch it. ... It has been suggested that this article or section be merged with fart. ... Constipation or irregularity, is a condition of the digestive system where a person (or animal) experiences hard feces that are difficult to eliminate; it may be extremely painful, and in severe cases (fecal impaction) lead to symptoms of bowel obstruction. ... Cyanocobalamin is a vitamin commonly known as vitamin B12 (or B12 for short). ...

Recently 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. (Laheij et al., 2004). An H2-receptor antagonist, often shortened to H2-antagonist, is a drug used to block the action of histamine on parietal cells in the stomach, decreasing acid production by these cells. ... It has been suggested that CURB-65 be merged into this article or section. ...

PPIs have also been shown to raise risk of CDF infection. ^[1] Binomial name Clostridium difficile Hall & OToole, 1935 Clostridium difficile ( ) (also referred to as C. diff or C-diff) is a species of bacteria of the genus Clostridium which are Gram-positive, anaerobic, spore-forming rods. ...

References

• AstraZeneca Pty Ltd. Nexium (Australian approved prescribing information). North Ryde: AstraZeneca; 2005.
• Katzung, BG. Basic & clinical pharmacology, 9th edition. New York : Lange Medical Books; 2004. ISBN 0-07-141092-9
• Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
• Laheij RJF, Sturkenboom MCJM, Hassing R-J, Dieleman J, Stricker BHC, Jansen JBMJ. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA 2004;292(16): 1955-60. PMID 15507580
• Wyeth Australia Pty Ltd. Zoton (Australian approved prescribing information). Baulkham Hills: Wyeth; 2004.
• PPIs raise risk of C. difficile infection

The Australian Medicines Handbook or AMH is a medical reference text commonly used in practice by health professionals (particularly general practitioners and pharmacists) in Australia. ... JAMA is the acronym for the Journal of the American Medical Association, a leading medical journal. ...