OMEPRAZOLE
Omeprazole is an effective treatment for several gastrointestinal disorders. These disorders include gastroesophageal reflux disease (GERD), peptic ulcers, gastric ulcers, duodenal ulcers, Zollinger-Ellison syndrome, and other stomach conditions. Omeprazole can also be used to prevent upper gastrointestinal bleeding in people who are at high risk for this condition. Omeprazole belongs to a class of drugs called proton pump inhibitors (PPIs) that works by reducing the amount of acid produced by the stomach. PPIs are some of the most effective medications available for treating GERD and other acid-related disorders. Omeprazole is available as an oral tablet, capsule, suspension, and can also be given by injection into a vein.
Omeprazole is considered safe, effective and well tolerated, with few side effects. However, like all medications, it does have some potential side effects, but they are generally mild and temporary. Common side effects of omeprazole include nausea, headaches, vomiting, abdominal pain, and increased intestinal gas. More serious side effects may include an increased risk of bone fractures, pneumonia, the potential of masking stomach cancer. However, the overall benefits of taking omeprazole outweigh the risks.
It is unclear if omeprazole is safe for use in pregnancy. Omeprazole should be used with caution in women who are pregnant or breastfeeding. Omeprazole works by blocking the release of stomach acid. This action reduces the amount of acid that is available to irritate the lining of the esophagus, stomach, or intestine. By reducing the amount of stomach acid, omeprazole can help to relieve the symptoms of GERD, peptic ulcer disease, and Zollinger-Ellison syndrome.
Omeprazole was patented in 1978 and a year later, in 1988 approved for medical use. Omeprazole is on the World Health Organization's List of Essential Medicines, and is considered one of the most important medications needed in a basic health system. Omeprazole is available in both over-the-counter and prescription forms.
Medical uses
Omeprazole works by reducing the amount of acid produced by the stomach and is used to treat gastroesophageal reflux disease (GERD), and it can also be used to treat other conditions involving the stomach, such as ulcers, especially those caused by H. pylori (Helicobacter pylori) bacteria, erosive esophagitis, Zollinger-Ellison syndrome, and eosinophilic esophagitis. Omeprazole is also used to treat frequent heartburn (occurring two or more times a week).
Gastroesophageal Reflux Disease (GERD)
Gastroesophageal reflux disease (GERD), also known as acid reflux, is a condition in which the stomach contents rise up into the esophagus (the tube that carries food from the mouth to the stomach).
The main symptom of GERD is heartburn. This is a burning sensation in the chest that can extend to the neck, throat, and jaw. Other symptoms include regurgitation (a feeling of food or liquid coming up into the throat or mouth), sour taste in the mouth, difficulty swallowing, chest pain, hoarseness, and cough.
Peptic ulcers
Peptic ulcers, gastric ulcers or duodenal ulcers are sores that develop in the stomach or duodenum, the first part of the small intestine. Ulcers can be caused by a number of factors, including infections, stress, genetic factors, by long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) but are usually caused by infection with the bacterium Helicobacter pylori.
The most common symptom of an ulcer is a burning sensation in the stomach or upper abdomen. Other symptoms include: bloating, belching, and nausea.
Erosive esophagitis
Erosive esophagitis is a condition that causes the lining of the esophagus to become irritated and inflamed. This can lead to pain, difficulty swallowing, and bleeding. Erosive esophagitis is often caused by stomach acid flowing back up into the esophagus. In some cases, surgery may be necessary to repair the damage caused by erosive esophagitis.
Zollinger-Ellison syndrome
Zollinger-Ellison syndrome is a rare digestive disorder in which the stomach produces too much gastric acid. This excess gastric acid can cause peptic ulcers and GERD. Zollinger-Ellison syndrome is caused by a tumor in the pancreas or small intestine that secretes gastrin, a hormone that stimulates the release of acid by the stomach. The tumor is usually noncancerous (benign), but in a small number of cases it may be cancerous (malignant).
Symptoms include abdominal pain, nausea, vomiting, weight loss, and diarrhea. If left untreated, there can be serious complications, but early diagnosis and treatment can help prevent complications.
Eosinophilic esophagitis
Eosinophilic esophagitis (EOE) is a chronic, immune-mediated inflammatory disease of the esophagus characterized by infiltration of eosinophils, a type of white blood cell. EOE affects people of all ages, but is most commonly diagnosed in children and young adults. The exact cause of EOE is unknown, but it is thought to be triggered by an allergic reaction to a food or other substance.
Common symptoms of EOE include difficulty swallowing (dysphagia), chest pain, heartburn, and food impaction (when food becomes stuck in the esophagus).
Adverse effects
- Central nervous system: headache (7%), dizziness (2%)
- Respiratory: upper respiratory tract infection (2%), cough (1%)
- Gastrointestinal: abdominal pain (5%), diarrhea (4%), nausea (4%), vomiting (3%), flatulence (3%), acid regurgitation (2%), constipation (2%)
- Neuromuscular and skeletal: back pain (1%), weakness (1%)
- Dermatologic: rash (2%)
Other concerns related to adverse effects of omeprazole are:
- Recurrence of Clostridium difficile associated diarrhea
- Osteoporosis-related fractures
- Hypomagnesemia
While omeprazole is generally considered to be a safe and effective medication, there are some potential side effects that should be considered. One of the most well-known potential side effects of omeprazole is that it may lead to vitamin B12 and iron malabsorption. Vitamin B12 and iron are essential nutrients that are necessary for many different functions in the body. If omeprazole leads to malabsorption of these nutrients, it could potentially cause serious health problems.
Another potential side effect of omeprazole is acute interstitial nephritis. This is a condition that causes inflammation of the kidneys. While this condition can be serious, it is important to note that it is relatively rare.
Overall, the potential side effects of omeprazole seem to be relatively insignificant. However, it is still important to be aware of them.
Long-term use
Long-term use of PPIs is strongly associated with the development of benign polyps from fundic glands (which is distinct from fundic gland polyposis). While these polyps do not cause cancer, they may resolve when PPIs are discontinued. There is no association between PPI use and cancer, but PPIs may mask gastric cancers or other serious gastric problems.
There is a possible association between long-term use and the development of dementia which requires further study to confirm.
There has been a lot of research done on the long-term effects of taking PPIs. Some of the effects include decreased calcium absorption (causing increased risk of osteoporosis and fractures), decreased magnesium absorption(causing electrolyte disturbances), and increased risk of certain infections such as C. difficile and community-acquired pneumonia. The reason for these effects is thought to be due to the decreased stomach acid production.
Pregnancy and breastfeeding
Omeprazole is considered the drug of second choice during pregnancy when antacids or ranitidine or cimetidine are no longer sufficient. There is some evidence that omeprazole may cross the placenta and enter the fetal circulation, but the clinical significance of this is not known. There is also a report of omeprazole being present in human milk, but again, the clinical significance is not known. Because of the lack of data on the use of omeprazole during pregnancy, it is generally recommended that the drug be used only when absolutely necessary. If it is necessary to use omeprazole during pregnancy, it is recommended that the lowest possible dose be used for the shortest possible duration.
Drug Interactions
Important drug interactions are rare. However, the most significant major drug interaction concern is the decreased activation of clopidogrel when taken together with omeprazole. Although still controversial, this may increase the risk of stroke or heart attack in people taking clopidogrel to prevent these events.
Drugs that depend on an acidic stomach environment (such as ketoconazole or atazanavir) may be poorly absorbed, whereas acid-labile antibiotics (such as erythromycin which is a very strong CYP3A4 inhibitor) may be absorbed to a greater extent than normal due to the more alkaline environment of the stomach.
St. John's wort (Hypericum perforatum) and Gingko biloba significantly reduce plasma concentrations of omeprazole through induction of CYP3A4 and CYP2C19.
Proton-pump inhibitors like omeprazole have been found to increase the plasma concentrations of methotrexate.
Pharmacology
Omeprazole irreversibly blocks the enzyme system on parietal cells that is needed for the secretion of gastric acid. This makes it a specific H+/K+ATPase inhibitor. This enzyme is needed for the final step in the secretion of gastric acid. By blocking this enzyme, omeprazole reduces the production of stomach acid.
Mechanism of action
Omeprazole is a selective and irreversible proton pump inhibitor. It suppresses stomach acid secretion by specific inhibition of the H+/K+-ATPase system found at the secretory surface of gastric parietal cells. Because this enzyme system is regarded as the acid (proton, or H+) pump within the gastric mucosa, omeprazole inhibits the final step of acid production in the stomach.
Omeprazole also inhibits both basal and stimulated acid secretion regardless of the stimulus as it blocks the last step in acid secretion. Omeprazole binds non-competitively so it has a dose-dependent effect.
The inhibitory effect of omeprazole occurs within 1 hour after oral administration. The maximum effect occurs within 2 hours. The duration of inhibition is up to 72 hours. When omeprazole is stopped, stomach acid secretion returns to baseline within 3 to 5 days. The inhibitory effect of omeprazole on acid secretion will plateau after 4 days of repeated daily dosing.
Pharmacokinetics
The absorption of omeprazole takes place in the small intestine and is usually completed within 3 to 6 hours. The systemic bioavailability of omeprazole after repeated doses is about 60%. Omeprazole has a volume of distribution of 0.4 L/kg. It has high plasma protein binding of 95%.
Omeprazole, as well as other PPIs, are only effective on active H+/K+-ATPase pumps. These pumps are stimulated in the presence of food to aid in digestion. For this reason, patients should be advised to take omeprazole with a glass of water on an empty stomach. Additionally, most sources recommend that after taking omeprazole, at least 30 minutes should be allowed to elapse before eating (at least 60 minutes for immediate-release omeprazole plus sodium bicarbonate products, such as Zegerid), though some sources say that with delayed-release forms of omeprazole, waiting before eating after taking the medication is not necessary.
Omeprazole is completely metabolized by the cytochrome P450 system, mainly in the liver, by CYP2C19 and CYP3A4 isoenzymes. Identified metabolites are the sulfone, the sulfide, and hydroxy-omeprazole, which exert no significant effect on acid secretion. About 77% of an orally given dose is excreted as metabolites in the urine, and the remainder is found in the feces, primarily originating from bile secretion. Omeprazole has a half-life of 0.5 to 1 hour. The pharmacological effects of omeprazole last longer as it is covalently bonded to proton pump on parietal cells to induce effects.
Chemistry
Omeprazole contains a tricoordinated sulfinyl sulfur in a pyramidal structure and therefore can exist as either the (S)- or (R)-enantiomers. Omeprazole is a racemate, an equal mixture of the two. In the acidic conditions of the canaliculi of parietal cells, both enantiomers are converted to achiral products (sulfenic acid and sulfenamide configurations) which react with a cysteine group in H+/K+ ATPase, thereby inhibiting the ability of the parietal cells to produce gastric acid.
AstraZeneca also developed esomeprazole (Nexium) which is a eutomer, purely the (S)-enantiomer, rather than a racem ate like omeprazole.
Omeprazole undergoes a chiral shift in vivo which converts the inactive (R)-enantiomer to the active (S)-enantiomer, doubling the concentration of the active form. This chiral shift is accomplished by the CYP2C19 isozyme of cytochrome P450, which is not found equally in all human populations. Those who do not metabolize the drug effectively are called “poor metabolizers”. The proportion of the poor metabolizer phenotype varies widely between populations, from 2.0 to 2.5% in African Americans and white Americans to >20% in Asians. Several pharmacogenomics studies have suggested that PPI treatment should be tailored according to CYP2C19 metabolism status.
Measurement in body fluids
Measurement of omeprazole in body fluids is important to monitor therapy or to confirm a diagnosis of poisoning in hospitalized patients. Plasma omeprazole concentrations are usually in a range of 0.2–1.2 mg/L in persons receiving the drug therapeutically by the oral route and 1–6 mg/L in people with acute overdose. Enantiomeric chromatographic methods are available to distinguish esomeprazole from racemic omeprazole.
History
Omeprazole was first made in 1979 by Swedish AB Hässle, part of Astra AB, now AstraZeneca. It was the first of the proton pump inhibitors (PPI). It was launched as an ulcer medicine under the name Losec.
Dosage forms
Omeprazole is available in strengths of 10, 20, 40, and in some markets 80 mg; and as a powder (omeprazole sodium) for intravenous injection. Most oral omeprazole preparations are enteric-coated, due to the rapid degradation of the drug in the acidic conditions of the stomach. This is most commonly achieved by formulating enteric-coated granules within capsules, enteric-coated tablets, and the multiple-unit pellet system (MUPS).
Trade names
Monopreparations
Acimax, Antra, Aspra, Audazol, Belmazol, Ceprandal, Danlox, Demeprazol, Desec, Dizprazol, Dudencer, Elgam, Emeproton, Emilok, Epirazole, Erbolin, Esomeprazole, Esomperazole, Exter, Gasec, Gastrimut, Gastrogard, Gastroloc, Gastrozol, Gibancer, Helicid, Helol, Indurgan, Inhibitron, Inhipump, Lensor, Logastric, Lomac, Losec, Losectil, Lozeprel, Mepral, Miol, Miracid, Mopral, Morecon, Nexiam, Nilsec, Nopramin, Nuclosina, Ocid, Olexin, Omapren, Omebeta, 20, Omecaps, Omed, Omefez, Omegast, Omepradex, Omepral, Omeprazen, Omeprazol, Omeprazon, Omeprazone, Omeprol, Omeprus, Omerprazole, Omesec, Omesek, Omez, Omezol, Omezolan, Omid, Omipiks, Omisec, Omitox, Omizac, Omizak, Ompanyt, Opal, Ortanol, Osiren, Ozid, Ozoken, Paprazol, Parizac, Pepticum, Pepticus, Peptilcer, Prazentol, Prazidec, Prazolit, Prilosec, Procelac, Proclor, Promez, Prysma, Ramezol, Regulacid, Romesek, Sanamidol, Secrepina, Segazole Sopral, Ulceral, Ulcesep, Ulcometion, Ulcozol, Ulcsep, Ulsen, Ultop, Ulzol, Victrix, Zefxon, Zegacid, Zegerid, Zepral, Zerocid, Zimor, Zoltum, and other generics.
Veterinary Medicine
GastroGard, Pepticure, Peptizole, Ulcergold.
EXPERT INFO
Quick Overview
Structure
Omeprazole 2D Structure
Omeprazole 3D Conformer – Ball and Stick
Omeprazole 3D Conformer – Sticks
Omeprazole 3D Conformer – Wire-Frame
Omeprazole 3D Conformer – Space-Filling
Commom Name
Omeprazole
Pronunciation
/oʊˈmɛprəzoʊl/
Latin Name
Omeprazolum
ATC Code - Anatomical Therapeutic Chemical Classification System
The Anatomical Therapeutic Chemical (ATC) Classification System is a drug classification system that classifies the active ingredients of drugs according to the organ or system on which they act and their therapeutic, pharmacological and chemical properties. Its purpose is an aid to monitor drug use and for research to improve quality medication use. It does not imply drug recommendation or efficacy. It is controlled by the World Health Organization Collaborating Centre for Drug Statistics Methodology (WHOCC).
CAS Registry Number
A CAS Registry Number, also referred to as CAS RN or informally CAS Number, is a unique identification number assigned by the Chemical Abstracts Service (CAS), US to every chemical substance described in the open scientific literature. It is a chemical database that includes organic and inorganic compounds, minerals, isotopes, alloys, mixtures, and nonstructurable materials (UVCBs, substances of unknown or variable composition, complex reaction products, or biological origin). CAS RNs are generally serial numbers (with a check digit), so they do not contain any information about the structures themselves the way SMILES and InChI strings do.
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Chemical Entities of Biological Interest, also known as ChEBI, is a chemical database and ontology of molecular entities focused on ‘small' chemical compounds, that is part of the Open Biomedical Ontologies (OBO) effort at the European Bioinformatics Institute (EBI). The term “molecular entity” refers to any “constitutionally or isotopically distinct atom, molecule, ion, ion pair, radical, radical ion, complex, conformer, etc., identifiable as a separately distinguishable entity”. The molecular entities in question are either products of nature or synthetic products which have potential bioactivity. Molecules directly encoded by the genome, such as nucleic acids, proteins and peptides derived from proteins by proteolytic cleavage, are not as a rule included in ChEBI.
ChEBI uses nomenclature, symbolism and terminology endorsed by the International Union of Pure and Applied Chemistry (IUPAC) and nomenclature committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB).
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ChemSpider
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CompTox Chemicals Dashboard (EPA)
The CompTox Chemicals Dashboard is a freely accessible online database created and maintained by the U.S. Environmental Protection Agency (EPA). The database provides access to multiple types of data including physicochemical properties, environmental fate and transport, exposure, usage, in vivo toxicity, and in vitro bioassay. EPA and other scientists use the data and models contained within the dashboard to help identify chemicals that require further testing and reduce the use of animals in chemical testing. The Dashboard is also used to provide public access to information from EPA Action Plans, e.g. around perfluorinated alkylated substances.
DrugBank
The DrugBank database is a comprehensive, freely accessible, online database containing information on drugs and drug targets created and maintained by the University of Alberta and The Metabolomics Innovation Centre located in Alberta, Canada. As both a bioinformatics and a cheminformatics resource, DrugBank combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information.
ECHA InfoCard
The ECHA supplies, via its website, a public summary of all the information it holds on the chemicals registered in its database. It provides this information in the form of a Substance Infocard giving hazards, uses and production or import quantities.[25] Information on over 245,000 chemicals is available, although most do not have full dossiers since they are used in amounts below one tonne per annum. The CAS Registry Number or the European Community number can be used to find substances in the online system. Other possible search terms include the international nonproprietary name (for pharmaceutical drugs), the ISO common name (for agrochemicals) or the IUPAC name.
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The IUPHAR/BPS Guide to PHARMACOLOGY is an open-access website, acting as a portal to information on the biological targets of licensed drugs and other small molecules. The Guide to PHARMACOLOGY (with GtoPdb being the standard abbreviation) is developed as a joint venture between the International Union of Basic and Clinical Pharmacology (IUPHAR) and the British Pharmacological Society (BPS). The Guide to PHARMACOLOGY aims to provide a concise overview of all pharmacological targets, accessible to all members of the scientific and clinical communities and the interested public, with links to details on a selected set of targets. The information featured includes pharmacological data, target, and gene nomenclature, as well as curated chemical information for ligands. Overviews and commentaries on each target family are included, with links to key references.
IUPAC Nomenclature of Chemistry
5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-benzimidazole
The International Union of Pure and Applied Chemistry (IUPAC) has published sets of rules to standardize chemical nomenclature. IUPAC nomenclature is used for the naming of chemical compounds, based on their chemical composition and their structure.
KEGG - Kyoto Encyclopedia of Genes and Genomes
KEGG (Kyoto Encyclopedia of Genes and Genomes) is a collection of databases dealing with genomes, biological pathways, diseases, drugs, and chemical substances. KEGG is utilized for bioinformatics research and education, including data analysis in genomics, metagenomics, metabolomics and other omics studies, modeling and simulation in systems biology, and translational research in drug development.
PDB - Protein Data Bank
The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cryo-electron microscopy, and submitted by biologists and biochemists from around the world, are freely accessible on the Internet via the websites of its member organisations (PDBe, PDBj, RCSB, and BMRB). The PDB is overseen by an organization called the Worldwide Protein Data Bank, wwPDB.
The PDB is a key in areas of structural biology, such as structural genomics. Most major scientific journals and some funding agencies now require scientists to submit their structure data to the PDB. Many other databases use protein structures deposited in the PDB. For example, SCOP and CATH classify protein structures, while PDBsum provides a graphic overview of PDB entries using information from other sources, such as Gene ontology.
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UNII - Unique Ingredient Identifier
The Unique Ingredient Identifier (UNII) is an alphanumeric identifier linked to a substance's molecular structure or descriptive information and is generated by the Global Substance Registration System (GSRS) of the Food and Drug Administration (FDA). It classifies substances as chemical, protein, nucleic acid, polymer, structurally diverse, or mixture according to the standards outlined by the International Organization for Standardization in ISO 11238 and ISO DTS 19844. UNIIs are non-proprietary, unique, unambiguous, and free to generate and use. A UNII can be generated for substances at any level of complexity, being broad enough to include “any substance, from an atom to an organism.”
Clinical Data
Drug Class
Proton pump inhibitors, ulcer therapeutics
Dosage Forms
capsules , enteric capsules, lyophilisate for solution for infusion, powder for solution for infusion, coated tablets
Routes of Administration
Areas of Application
Bioavailability
Protein binding
Metabolism
Elimination half-life
Excretion
- 80% (urine)
- 20% (bile via feces)
Formula
Molar Mass
Chirality
Density
Melting Point
Solubility
19mg mL – 1 DMSO
4.5 mg mL – 1 ethanol
SMILES
InChI
Key: SUBDBMMJDZJVOS-UHFFFAOYSA-N
References