Omeprazole

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Omeprazole

Systematic (IUPAC) name
(RS)-6-methoxy-2-((4-methoxy-3,5-dimethylpyridin-2-yl) methylsulfinyl)-1H-benzo[d]imidazole
Identifiers
CAS number	73590-58-6
ATC code	A02BC01
PubChem	4594
DrugBank	APRD00446
ChemSpider	4433
Chemical data
Formula	C17H19N3O3S
Mol. mass	345.4 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	35–60%
Metabolism	Hepatic (CYP2C19, CYP3A4)
Half life	1 - 1.2 hours
Excretion	80% Renal 20% Faecal
Therapeutic considerations
Pregnancy cat.	B3(AU) C(US)
Legal status	Prescription Only (S4)(AU) POM(UK) OTC(US)
Routes	Oral, IV
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Omeprazole (INN) (pronounced /oʊˈmɛprəzoʊl/) is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD/GERD) and Zollinger-Ellison syndrome. It was first marketed in the US in 1989 by AstraZeneca as the magnesium salt omeprazole magnesium under the brand names Losec and Prilosec, and is now also available from generic manufacturers under various brand names. Omeprazole is one of the most widely prescribed drugs internationally and is available over the counter in some countries.

Contents 1 Pharmacology 2 Name change 3 Clinical use 3.1 Use in Helicobacter pylori eradication 4 Dosage forms 4.1 Multiple unit pellet system 4.2 Immediate release formulation 5 Side effects 6 Interactions 7 Absorption and distribution 8 Metabolism and excretion 9 References

[edit] Pharmacology

Omeprazole is a racemate. It contains a tricoordinated sulfur atom in a pyramidal structure and therefore can exist in equal amounts of both the S and R enantiomers. In the acidic conditions of the stomach, both are converted to achiral products, which reacts with a cysteine group in H⁺/K⁺ ATPase, thereby inhibiting the ability of the parietal cells to produce gastric acid.

Facing the loss of patent protection and competition from generic drug manufacturers, AstraZeneca developed and heavily marketed esomeprazole (Nexium) as a replacement^[when?]. Esomeprazole is the S-enantiomer in the pure form.

According to AstraZeneca, 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 approximate proportion of the poor metabolizer phenotype in different populations is as follows:^{[citation needed]}

• Caucasians 10%
• Asian 20%
• South Pacific Islands 70%

In theory, by using pure esomeprazole the effect on the proton pump will be equal in all patients, eliminating the "poor metabolizer effect".^{[citation needed]}

[edit] Name change

In 1990, at the request of the United States Food and Drug Administration (FDA), the brand name Losec was changed to Prilosec to avoid confusion with the diuretic Lasix (furosemide).^[1] Unfortunately, the new name has led to confusion between omeprazole (Prilosec) and fluoxetine (Prozac), an antidepressant.^[1]

[edit] Clinical use

[edit] Use in Helicobacter pylori eradication

Omeprazole is combined with the antibiotics clarithromycin and amoxicillin (or metronidazole in penicillin-hypersensitive patients) in the 7-14 day eradication triple therapy for Helicobacter pylori. Infection by H. pylori is the causative factor in the majority of peptic and duodenal ulcers.^{[citation needed]}

[edit] Dosage forms

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Omeprazole is available as tablets and capsules (containing omeprazole or omeprazole magnesium) in strengths of 10 mg, 20 mg, and in some markets 40 mg and 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.

It is also available for use in injectable form (I.V.) in Europe, but not in the U.S. The injection pack is a combination pack consisting of a vial and a separate ampule of reconstituting solution. Each 10 ml clear glass vial contains a white to off-white lyophilised powder consisting of omeprazole sodium 42.6 mg equivalent to 40 mg of omeprazole.

[edit] Multiple unit pellet system

Omeprazole tablets manufactured by AstraZeneca (notably Losec/Prilosec) are formulated as a "multiple unit pellet system" (MUPS). Essentially, the tablet consists of extremely small enteric-coated granules (pellets) of the omeprazole formulation inside an outer shell. When the tablet is immersed in an aqueous solution, as happens when the tablet reaches the stomach, water enters the tablet by osmosis. The contents swell from water absorption causing the shell to burst, releasing the enteric-coated granules. For most patients, the multiple-unit pellet system is of no advantage over conventional enteric-coated preparations. Patients for which the formulation is of benefit include those requiring nasogastric tube feeding and those with difficulty swallowing (dysphagia).^{[citation needed]}

The granules are manufactured in a fluid air bed system. Sugar spheres in suspension are sequentially sprayed with aqueous suspensions of omeprazole, a protective layer, an enteric coating and an outer layer to reduce granule aggregation. The granules are mixed with other excipients and compressed into tablets. Finally, the tablets are film-coated to improve the stability and appearance of the preparation.

[edit] Immediate release formulation

In June 2004 the FDA approved an immediate release preparation of omeprazole and sodium bicarbonate that does not require an enteric coating. This preparation employs sodium bicarbonate as a buffer to protect omeprazole from gastric acid degradation. This allows for the production of chewable tablets. This combination preparation is marketed in the United States by Santarus under the brand name Zegerid. Zegerid is marketed as capsules, chewable tablets, and powder for oral suspension. Zegerid is most useful for those patients who suffer from nocturnal acid breakthrough (NAB) or those patients who desire immediate relief. In India it is marketed by Dr. Reddy's Laboratories as powder formulation with the brand name OMEZ-INSTA. It is reported to have additional benefits with patients suffering from alcoholic gastritis and life-style associated gastritis.^{[citation needed]}

[edit] Side effects

Some of the most frequent side effects of omeprazole (experienced by over 1% of those taking the drug) are headache, diarrhea, abdominal pain, nausea, dizziness, trouble awakening and sleep deprivation, although in clinical trials the incidence of these effects with omeprazole was mostly comparable to that found with placebo.^[2]

Proton pump inhibitors may be associated with a greater risk of hip fractures,^[3][4][5] and clostridium difficile-associated diarrhea.^[6] Patients are frequently administered the drugs in intensive care as a protective measure against ulcers, but this use is also associated with a 30% increase in occurrence of pneumonia.^[7]

Other side effects may include bone rebuild interference and B12 vitamin reduction.^{[citation needed]}

[edit] Interactions

B12 deficiencies can lead to hair loss. http://www.healthguidance.org/entry/6957/1/B12-Vitamin-Deficiency-and-Hair-Loss.html

Patients who are taking Plavix (clopidogrel) in combination with proton pump inhibiting drugs may be at a greater risk of stroke or heart attack <Medco Health Solutions, Inc., 2005-2006 study of 14,000 patient records>. As with most proton pump inhibitors, omeprazole is also a p-glycoprotein inhibitor and may open the blood-brain barrier, causing unwanted interactions. This is especially notable when combined with loperamide.

Severe common allergic reactions (rash, hives, itching, difficulty breathing, tightness in the chest, swelling of the mouth, face, lips or tongue, unusual hoarseness), chest pain, dark urine, fast or irregular heartbeat fever, chills, or a sore throat, red, swollen, blistering or peeling skin, seizures, swelling of the hands, ankles or feet, easy bruising or unusual bleeding, increased unusual or sudden weight gain, unusual tiredness, vision changes, yellow eyes or skin.

Gastro-intestinal Gastric polyposis, have been reported in three of the eleven patients treated with prolonged treatment with omeprazole (20 to 40 mg per day). Cast Iron gland and hyperplastic polyps develop in the stomach of these patients. Neither dysplasia nor malignancy was present. The significance of the results of a small number of cases is unknown. Controlled studies are needed to fully evaluate this effect.

Endocrine Endocrine side effects included gynecomastia, breast augmentation and breast in women.

Reduced Side effects included increased liver transaminases, alkaline phosphatase, bilirubin, and rare cases of hepatitis and hepatic encephalopathy. Fatal fulminant hepatic failure due to omeprazole has also been reported.

Haematological Haematological side effects included rare cases of haemolytic anemia, pancytopenia, neutropenia, thrombocytopenia, anemia, agranulocytosis and leukocytosis.

Respiratory Respiratory adverse effects include cough, and rare cases of epistaxis and sore throat.

Nervous Side effects on the nervous system including headaches, dizziness, drowsiness, dizziness, facial numbness and dysesthesia, paresthesia of the extremities, and a report of the corridor reversible ataxia.

Cardio-vascular The cardiovascular side effects are rarely reported. These include angina pectoris, tachycardia, bradycardia, palpitations, high blood pressure and peripheral edema.

Hypersensitivity Side effects have included allergic urticaria and angioedema. A case report of anaphylaxis in half use of omeprazole has been documented.

Metabolic The metabolic effects include hypoglycemia, hyponatremia, weight gain and elevated levels of uric acid. It was also reported that omeprazole May cause hypomagnesemia with hypocalcemia and hypokalemia. A case report of omeprazole in combination with symptomatic hyponatremia, probably secondary to inappropriate secretion of ADH reported.

Psychiatric Psychiatric adverse events were rarely reported. These include depression, nervousness, hallucinations, insomnia, anxiety, dreams, and apathy.

Urogenital Urogenital side effects include impotence and rare cases of urinary tract infection, pyuria, urinary frequency, proteinuria, hematuria, glucosuria, and testicular pain.

Skeletal Muscles Adverse muscle including the development of a non-specific arthritis, which appears to resolve after withdrawal of omeprazole. Hip fracture have been reported. At least one case of severe acute myopathy has been reported. The risk of hip fracture was significantly increased in patients prescribed long-term high dose PPI.

Immunological Immunological reactions were rarely reported. These include a single case of an autoimmune disease with the development of fever, joint pain, Raynaud’s phenomenon, and as a positive ANA. With right dose and always consult to doctor, will help to avoid more serious effect when using Omeprazole. source : http://cleanroad.info/omeprazole-side-effect.html

[edit] Absorption and distribution

The absorption of omeprazole takes place in the small intestine and is usually completed within 3–6 hours. The systemic bioavailability of omeprazole after repeated dose is about 60%. Omeprazole bioavailability is significantly impaired by the presence of food and, therefore, patients should be advised to take omeprazole before eating. Plasma protein binding is about 95%.

[edit] Metabolism and excretion

Omeprazole is completely metabolized by the cytochrome P450 system, mainly in the liver. Identified metabolites are the sulfone, the sulfide and hydroxy-omeprazole, which exert no significant effect on the acid secretion. About 80% 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.

[edit] References