What Is Omeprazole?

Omeprazole is mainly used for duodenal ulcers and Zhuo-Ellison syndrome. It can also be used for gastric ulcer and reflux esophagitis. Intravenous injection can be used for the treatment of peptic ulcer acute bleeding. Combined with amoxicillin and clindamycin or metronidazole and clarithromycin to kill H. pylori.

Drug Name: 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl) methyl] sulfinyl] -1H-benzimidazole
Drug type: Essential medicines
Drug name: Omeprazole

English name: Omeprazole
Chinese alias: Sulfoxide imidazol; mesoprazole; trimethoprim;
English alias: Losec; Mopral
Molecular formula: C17H19N3O3S
Molecular weight: 345

Omeprazole compounds

Omeprazole Basic Information

Chinese name: omeprazole

Chinese alias: Esomeprazole Magnesium Impurity F; Oke; Omeprazole; Oxicon; Fordme Omeprazole; Losec; Omega Sulfoxide; Wobidazole; Omidiprazole; Ya Miprazole; Sulfurimidazole; Amperazol; Mesosulfazole

English name: (R) -omeprazole

English alias: LOSEC; MEPRAL; GASTROGARD; OMEPRAZOLE; Loec; Moprial; Omeprazolum

CAS number: 119141-89-8

Molecular formula: C ₁₇ H ₁₉ N ₃ O ₃ S

Structural formula:

Molecular weight: 345.41600

Exact mass: 345.11500

PSA: 96.31000

LogP: 3.76540

Omeprazole physical and chemical properties

Appearance and properties: white or off-white crystalline powder; odorless; easy to change color when exposed to light. Easily soluble in dichloromethane, slightly soluble in methanol or ethanol, slightly soluble in acetone, insoluble in water; soluble in 0.1 mol / L sodium hydroxide solution.

Density: 1.37 g / cm ¹

Boiling point: 600ºC at 760 mmHg

Flash point: 316.7ºC

Storage conditions: 2-8ºC

Omeprazole Safety Information

Customs Code: 2941500000

Danger category code: R36 / 37/38

Safety instructions: S26; S36

Dangerous goods sign: Xi ^[2]

Omeprazole Pharmacopoeia Standard

[Source (name), content (potency)]

This product is 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl) methyl] sulfinyl] -1H-benzimidazole. Calculated on dry basis, containing C ₁₇ H ₁₉ N ₃ O ₃ S shall not be less than 98.5%.

[Character]

This product is white or off-white crystalline powder; odorless; easy to change color when exposed to light.

This product is soluble in dichloromethane, slightly soluble in methanol or ethanol, slightly soluble in acetone, insoluble in water; soluble in 0.1mol / L sodium hydroxide solution.

[Identification] (1) Take about 3mg of this product, add 3ml of 0.1mol / L sodium hydroxide solution to dissolve, add 1ml of silicotungstic acid test solution, shake well, add a few drops of dilute hydrochloric acid, and it will produce white flocculent precipitate . (2) Take this product, add 0.1 mol / L sodium hydroxide solution to make a solution containing about 15 g per 1 ml, and measure it according to the ultraviolet-visible spectrophotometry (Appendix IV A). It has a wavelength of 276nm and 305nm. Maximum absorption, minimum absorption at wavelengths of 256nm and 281nm. (3) The infrared light absorption spectrum of this product should be consistent with the control spectrum (spectrum set 675).

[Check] Clarity and color of dichloromethane solution: Take 0.5g of this product, add 25ml of dichloromethane to dissolve, and the solution should be clear and colorless; if color develops, apply UV-visible spectrophotometry immediately (Appendix IV A), The absorbance shall be measured at a wavelength of 440 nm, and shall not exceed 0.10. Related substances are protected from light. Take an appropriate amount of this product, and use the mobile phase to make about 0.2mg of the test solution per 1ml and about 2g of the control solution in each ml; take 1mg of omeprazole reference substance and omeprazole sulfonylate (5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl) -methyl] -sulfonyl] -1H benzimidazole) reference substance 1mg, add The mobile phase was dissolved to 10 ml, shaken, and 20 l was injected into the liquid chromatograph, and measured according to high performance liquid chromatography (Appendix VD), using octyl-methane-bonded silica gel as a filler; 0.1 mol / L hydrogen phosphate Sodium solution (pH adjusted to 7.6 with phosphoric acid)-acetonitrile (75:25) as mobile phase; detection wavelength is 280nm; theoretical number of plates calculated from omeprazole peak is not less than 2000, omeprazole peak and omeprazole The resolution of the azole sulfonate peak should be greater than 2.0. Take the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 15% of the full range; and then accurately measure 20 l each of the test solution and the control solution, and inject them into the liquid chromatograph respectively. Record the chromatogram to 3 times the peak retention time of the main component. If there is an impurity peak in the chromatogram of the test solution, the area of a single impurity peak must not be greater than 0.3 times (0.3%) the area of the main peak of the control solution, and the sum of the area of each impurity peak must not be greater than the area of the main peak of the control solution (1.0%). Residual solvents: methanol, acrylic acid, acetonitrile, methylene chloride and toluene. Take about 0.3g of this product, weigh it accurately, put it in a 10ml headspace bottle, add 3ml of dimethylformamide to dissolve it, and seal it. Solution; take an appropriate amount of methanol, acetone, acetonitrile, dichloromethane and toluene, accurately weigh, add dimethylformamide to dissolve and quantitatively dilute to make 0.3ml methanol, 0.5mg acetone, 41g acetonitrile per 1ml, A mixed solution of 60 g of methylene chloride and 89 g of toluene was accurately weighed into 3 ml, placed in a 10 ml headspace bottle, sealed, and used as a reference solution. Capillary chromatographic column with 6% propyl phenyl-94% dimethylpolysiloxane (or similar polarity) as the fixed solution according to the test of residual solvent (Appendix P second method); starting temperature 50 ° C; maintained for 7 minutes, heated to 110 ° C at a rate of 15 ° C per minute, and then heated to 190 ° C at a rate of 20 ° C per minute for 5 minutes; the inlet temperature was 150 ° C; the detector temperature was 220 ; headspace bottle equilibrium temperature is 95 ° C, equilibration time is 45 minutes. Take the reference solution headspace sample, and the resolution of each component peak should meet the requirements. Then take the test solution and the reference solution for headspace injection, record the chromatogram, and calculate the peak area according to the external standard method, which should meet the requirements. Take this product for weight loss and dry it under reduced pressure at 60 ° C for 4 hours. The weight loss should not exceed 0.5% (Appendix L). Take 1.0g of this product and check it according to law (Appendix N). The remaining residue should not exceed 0.1%. The heavy metal shall be taken as the residue left under the burning residue, and shall be inspected in accordance with the law (Appendix H Second Law). The content of heavy metal shall not exceed 20 parts per million.

[Content determination] Take about 0.2g of this product, accurately weigh, add 50ml of ethanol-water (4: 1) to dissolve, according to potentiometric titration (Appendix A), use sodium hydroxide titration solution (0.1mol / L ) Titration. Each 1 ml of sodium hydroxide titration solution (0.1 mol / L is equivalent to 34.54 mg of C ₁₇ H ₁₉ N ₃ O ₃ S.

[Category] Proton pump inhibitors.

[Storage] shading, sealed, and stored in a dry and cold place ^[3] .

Omeprazole Drug Description

Omeprazole classification

Digestive System Drugs> Acid and Gastric Mucosal Protection

Omeprazole traits

It is a white to off-white crystalline powder with a melting point of 156 ° C.

Omeprazole dosage form

1. Capsule: 20mg;

2. Injection (powder): 40mg;

3. Injection: 40mg.

Omeprazole Pharmacology

It is a proton pump inhibitor and a fat-soluble weakly alkaline drug. Easy to concentrate in the acidic environment, and specifically act on the secretory microtubules formed by the apical membrane of the gastric mucosal wall cells and the tubular vesicles in the cytoplasm, that is, where the proton pump of the gastric wall cells (H ⁺ , K ⁺ -ATPase) is located Site, and converted into the active form of sulfinamide, through the disulfide bond and the thiol group of the proton pump to irreversibly bind, thereby inhibiting the activity of H +, K ⁺ -ATPase, blocking the last step of gastric acid secretion, making parietal cells The H ⁺ in the stomach cannot be transported into the gastric cavity, so that the acid content in gastric juice is greatly reduced. It has a strong inhibitory effect on basal gastric acid and gastric acid secretion caused by stimulation. It has a significant inhibitory effect on histamine, pentagastrin and gastric acid secretion caused by stimulation of the vagus nerve. It also has a strong and lasting inhibitory effect on gastric acid secretion caused by dibutylcycloadenylic acid, which cannot be inhibited by H2 receptor antagonists. With the obvious decrease in gastric acid secretion after administration, the gastric pH increased rapidly. Faster relief of heartburn and pain. The cure rate for duodenal ulcer is also higher, and the recurrence rate is lower.

Omeprazole pharmacokinetics

Omeprazole is rapidly absorbed orally through the small intestine and takes effect within 1 hour. Food can delay its absorption but does not affect the total absorption. Different administration methods, dosage forms, and the number of medications can affect the blood drug concentration and bioavailability of the drug in the body. Omeprazole has a bioavailability of about 35% in a single dose and 60% in repeated doses. Omeprazole reached a peak blood concentration of 0.5 to 7 hours after oral administration, and the peak concentration was 0.22 to 1.16 mg / L. Omeprazole is mainly bound to plasma proteins after absorption into the blood, and its plasma protein binding rate is 95% to 96%. Omeprazole can be distributed to liver, kidney, stomach, duodenum, thyroid and other tissues. When the equilibrium is reached, the volume of distribution is 0.19 ~ 0.48L / kg, which is equivalent to extracellular fluid. Omeprazole is not easy to penetrate blood- Cerebrospinal fluid barrier, but easily through the placenta, omeprazole is completely oxidized and metabolized by the liver microsomal cytochrome P450 oxidase system in the body. There are at least 6 metabolites, mainly 5-hydroxyomeprazole, Meprazole sulfone and a small amount of omeprazole sulfide. Omeprazole is almost completely eliminated in the body in a metabolic manner. The elimination half-life of plasma is 0.5 to 1 hour, and 3 hours in patients with chronic liver disease. The plasma concentration disappears substantially 4 to 6 hours after administration, of which about 72% to 80%. Metabolites are excreted by the kidney, and another 18% to 23% of the metabolites are secreted by the bile and excreted in the feces. Regardless of single or multiple dosing, there are obvious individual differences in oxidative metabolism of omeprazole, mainly manifested by the low or defective ability of the drug's hydroxylation metabolism in some individuals, which makes the prototype drug elimination slow and the elimination half-life extended. The AUC increased significantly ^[1] .

Omeprazole indications

1. For gastric ulcer and duodenal ulcer. Omeprazole is used in combination with antibiotics in combination of two and three regimens for the treatment of peptic ulcer associated with Helicobacter pylori (HP).

2. For reflux esophagitis and gastrinoma (Zollinger-Ellison syndrome).

3. Omeprazole intravenous injection can be used for the treatment of acute bleeding of peptic ulcer, such as acute gastric mucosal lesion bleeding.

Omeprazole dosage

1. (1) Stomach and duodenal ulcers: 20mg each time, once in the morning. Duodenal ulcer treatment usually takes 2 to 4 weeks, and gastric ulcer treatment takes 4 to 8 weeks. For patients with refractory ulcers, 20mg each time, twice a day or 40mg each time, once a day. (2) Reflux esophagitis: 20 ~ 60mg once a day. (3) Zhuo-Ai syndrome: The initial dose is 60 mg each time, once a day, and the condition can be adjusted to a dose of 20 to 120 mg per day to control symptoms. If the dose is greater than 80 mg per day, it should be administered in two divided doses.

2. Intravenous injection: For the treatment of peptic ulcer bleeding, intravenous injection can be given at a dose of 40 mg each time, once every 12 hours for 3 consecutive days. The first dose can be doubled.

3. Intravenous infusion: Those who have a large amount of bleeding can also use the first dose of 80mg intravenous infusion, and then change to 8mg per hour to maintain until the bleeding stops.

4. Dose for liver dysfunction: Use with caution when severe liver dysfunction, halving the dose if necessary.

Omeprazole adverse reactions

1. May have dry mouth, mild nausea, vomiting, bloating, constipation, diarrhea, abdominal pain, etc .; alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin also occur. It is usually mild and transient, and most do not affect treatment. In addition, foreign data report that atrophic gastritis can be observed in gastric biopsy specimens of patients treated with omeprazole for a long time.

2. Neuropsychiatric system: may have paresthesia, dizziness, headache, drowsiness, insomnia, peripheral neuritis, etc.

3. Metabolic / endocrine system: Long-term use of omeprazole can lead to vitamin B12 deficiency.

4. Carcinogenicity: Animal experiments have shown that omeprazole can cause proliferation of intestinal chromaffin cells, the main endocrine cells in the bottom of the stomach and the body of the stomach. Long-term medication can also cause gastric carcinoids.

5. Others: There may be rash, male mammary gland development, hemolytic anemia, etc.

Omeprazole contraindications

1. Those who are allergic to omeprazole.

2. Severe renal insufficiency.

3. Infants and young children.

4. Banned for pregnant women and lactating women.

Omeprazole precautions

(1) It has been reported abroad that the performance of atrophic gastritis can be observed in gastric biopsy specimens of patients who use this product for a long time. Long-term use may cause hypergastrinemia and may also lead to vitamin B12 deficiency. (2) Animal experiments show that this product can cause intestinal chromaffin cells in the bottom of the stomach and the body of the stomach to grow, and long-term medication may cause gastric carcinoids. (3) Patients with severe liver dysfunction should be used with caution, and the dose should be halved if necessary.

Omeprazole drug interactions

1. Omeprazole can improve the bioavailability of pancreatic enzymes and enhance its efficacy; the combination of the two has a good effect on refractory fatty diarrhea caused by pancreatic cystic fibrosis and functional diarrhea after extensive small bowel resection.

2. Drugs sensitive to Helicobacter pylori (such as amoxicillin, etc.) combined with omeprazole have a synergistic effect, which can improve the efficacy.

3. Omeprazole has an enzyme inhibitory effect when combined with drugs metabolized by the liver cytochrome P450 system (such as dicoumarin, warfarin, diazepam, phenytoin, nifedipine, etc.), which can make the latter The half-life is prolonged and metabolism is slowed. However, at general clinical doses, omeprazole has a small effect, and its pharmacokinetic effect on theophylline and antipyrine is much smaller than that of cimetidine, and it has no clinical effect on warfarin. significance.

4. When omeprazole is used in combination with calcium antagonists, the clearance of both drugs in vivo is slow, but it has no clinical significance.

5. Omeprazole can inhibit the conversion of prednisone into the active form and reduce its efficacy.

6. Omeprazole can cause a low-acid environment, so that digoxin is less converted into actives, reducing its efficacy. Digoxin dose should be adjusted shortly after taking omeprazole and its withdrawal.

7. Omeprazole's acid suppression can affect iron absorption.

8. Omeprazole can make the stomach in an alkaline environment, making tetracycline difficult to absorb, the absorption of ampicillin and ketoconazole is also reduced, and the blood concentration is reduced.

9. Omeprazole can affect the plasma concentration (increased or decreased) of environmental cyclosporine, and the mechanism is unknown.

10. Omeprazole can change the pH value in the stomach, so that the sustained-release and controlled-release preparations are destroyed, and the drug dissolution is accelerated.

11. Omeprazole inhibits gastric acid and increases the total number of bacteria in the stomach, leading to the conversion of nitrite to carcinogenic nitrite; combined with vitamin C or E may limit the formation of nitrite compounds.

12. During the use of triazolam, lorazepam, or fluoxetine, omeprazole administration can cause gait disorders, and it can return to normal after stopping one drug. ^[1]

Omeprazole poisoning

Omeprazole (Losec) is a proton pump inhibitor. It is mainly used for the treatment of duodenal ulcers and Zhuo-Ai syndrome. It can also be used for gastric ulcers and reflux esophagitis. After oral administration of this drug, about 42% are excreted within 2 hours, and 83% of the total excreted from urine in 96 hours. The oral half-life is 0.4 hours, and the plasma protein binding rate is about 95%. Intravenous or oral administration, commonly used at 1 / d, 20 mg each time. Poisoning mainly affects the liver, kidneys, nervous system, respiratory system, cardiovascular system and blood system.

Clinical manifestation

1. Adverse reactions are mainly nausea, flatulence, diarrhea, constipation, epigastric pain, etc. Rashes, ALT, and bilirubin elevations also occur, and are generally mild and transient, and most do not affect treatment.

2. Poisoning can occur when taking this medicine for a long time or taking a large amount by mistake, the main manifestations are as follows:

(1) Effects on the liver: transient serum aminotransferase and alkaline phosphatase may be elevated.

(2) Damage to the kidney: elevated proteinuria, urea nitrogen and creatinine, occasionally interstitial nephritis or renal failure.

(3) Symptoms of the nervous system: headache, tinnitus, drowsiness, anxiety, depression, peripheral neuropathy in some patients, and numbness of the fingers.

(4) Respiratory symptoms: Individual patients may develop cough, asthma, and acute pulmonary edema.

(5) Cardiovascular system symptoms: bradycardia (or tachycardia), right bundle branch block.

(6) Blood: Leukocyte and thrombocytopenia, even whole blood cell decrease and hemolytic anemia.

(7) Others: occasionally visual impairment, subacute myositis, progressive muscle weakness, and difficulty walking.

diagnosis

The main points of diagnosis of omeprazole poisoning are:

With the history of omeprazole application, the above manifestations appear.

treatment

The main points of treatment for omeprazole poisoning are:

1. General adverse reactions occur, and most of them can gradually recover on their own.

2. Allergic reactions were treated with antihistamines and glucocorticoids.

3. Symptomatic and supportive treatment ^[4] .

Omeprazole Expert Reviews

Omeprazole was the first proton pump inhibitor to be introduced. It has a strong inhibitory effect on gastric acid, and its curative effect is better than H2 receptor antagonist and prostaglandin E2, sucralfate, colloidal bismuth and high-dose antacid, which can rapidly improve the symptoms of peptic ulcer and reflux esophagitis. There have been no reports of gastric mucosal changes after long-term use of the drug.

^[1] ^[5-7]