Omeprazole

The Food and Drug Administration approved omeprazole in 1989. Omeprazole, a proton pump inhibitor, is used to treat stomach acid issues. These illnesses include gastro-oesophageal reflux disease and peptic ulcer disease, both of which are distinguished by high stomach acid production. This was the first therapeutically effective drug in its class, and its approval prompted the development of several other proton pump inhibitor medicines. 

Omeprazole was generally effective and well tolerated, so it became widely used in both children and adults. Proton pump inhibitors are used to treat GERD symptoms like heartburn and hypersecretion, as well as to promote tissue healing and ulcers caused by gastric acid and H. pylori infections. 

BRAND NAME:

Prilosec – Main ingredient is omeprazole. It is available in the form of omeprazole delayed-release tablets 20 mg/ acid reducers.

MECHANISM OF ACTION:

Omeprazole is a proton pump inhibitor. It is a substituted benzimidazole from the antisecretory class of chemicals. It inhibits the parietal cell's H+/K+ ATP pump,  the final step in acid generation. Omeprazole, in turn, suppresses gastric basal and increases acid secretion. Omeprazole's inhibitory effects begin quickly within an hour of treatment, with the highest effect happening after two The inhibitory effect lasts for approximately 72 hours after administration, followed by a return to baseline activity in 3 to 5 days. The effects will plateau on the fourth day with daily use of the medication. Omeprazole is extensively metabolized by the hepatic cytochrome P450 enzyme system, mainly via CYP2C19 and CYP3A4 isozymes. However, the pharmacological effect of omeprazole lasts much longer as the drug preferentially concentrates in parietal cells, where it forms a covalent linkage with H+/K+ ATPase, which is irreversibly inhibited.

PHARMACOKINETICS:

Absorption: Delayed-release omeprazole capsules contain enteric-coated granules that only release omeprazole once the drug leaves the stomach. Once the drug is released, it is rapidly absorbed. It has an absolute bioavailability of 30 to 40%, and the peak plasma concentration is attained in 0.5 to 3.5 hours, peak plasma concentration and AUC are increased proportionally up to 40 mg. However, due to saturation of the first pass effect above a 40 mg dose, those increase greater than linear at a dose above 40 mg. 

Distribution: Omeprazole has a mean volume of distribution of around 0.3L/kg. 

Metabolism: Omeprazole is extensively metabolized in the liver by the cytochrome P450 enzyme system. The majority of its metabolism is dependent on the polymorphically expressed CYP2C19, which is responsible for the formation of hydroxyl omeprazole, the primary metabolite detected in plasma. The remainder is dependent on CYP3A4, which is responsible for the production of omeprazole sulphone.

Excretion: It is eliminated mainly in urine as an unchanged drug and its metabolites. Its plasma half-life is 0.5 to 1 hour after oral administration in a healthy subject.

PHARMACODYNAMICS:

Omeprazole, administered orally at doses of 30 or 40 mg for 2-4 weeks, did not affect thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone, cortisol, oestradiol, testosterone, prolactin, cholecystokinin, or secretinhis. The medicine reduces gastric acid output. After oral administration, the antisecretory effect of omeprazole usually begins within one hour, with the maximal effect happening two hours later. Omeprazole's inhibitory effects on acid secretion increase with repeated once-daily doses, eventually reaching a plateau after four days. 

DOSAGE AND ADMINISTRATION:

Omeprazole is available as Prilosec, Prilosec OTC, and generic omeprazole in the following dosage forms that are taken by mouth

•        10mg, 20 mg, 40 mg oral capsule

•        20 mg oral tablets

•        20 mg orally disintegrating tablets

•        2.5 mg, 10 mg packets of powder for oral suspension

The administration route for omeprazole heavily depends on the diagnosis of a medical condition and the patient’s preferred orally disintegrating tablets.                                                                                                                                                                                                         

The recommended oral dose for treating symptomatic GERD absent esophageal lesions is 20 mg daily for up to 4 weeks. However, therapy may extend to 8 weeks if erosive lesions are present.

 DRUG INTERACTIONS:

Omeprazole may interact with

• clopidogrel, a blood thinner used to treat blood clots

• cilostazol, a medication used to alleviate intermittent claudication symptoms.

• Citalopram is a medication used to treat depression.

• Methotrexate 

• Digoxin is a medication used to treat irregular heartbeat and heart failure.

• Anti-retroviral medications (rilpivirine, nelfinavir, or saquinqvir) 

• Rifampin for tuberculosis.

Co-administration with amoxicillin- combine therapy of omeprazole and amoxicillin may lead to serious fatal hypersensitivity reactions in patients on penicillin therapy. These reactions are most common in patients with a history of hypersensitivity reactions to penicillin,  cephalosporins, or other allergens. During combined therapy, if such reactions occur amoxicillin therapy should be discontinued and appropriate therapy should be implemented.

Co-administration with clarithromycin: combine therapy of omeprazole and clarithromycin may increase the plasma levels of omeprazole and clarithromycin.

CONTRAINDICATIONS:

Omeprazole is contraindicated in patients with a history of hypersensitivity to the drug or any excipients form. Hypersensitivity reactions like anaphylactic shock, angioedema, interstitial nephritis, anaphylaxis, urticarial, and bronchospasm may occur. According to product labeling omeprazole is contraindicated in patients taking dosage forms containing rilpivirine.

SIDE EFFECTS:

The most common side effects of omeprazole are listed below

•        Headache

•        Stomach pain

•        Nausea

•        Diarrhea

•        Vomiting

•        Infection in the nose or throat

•        fever

Serious side effects of omeprazole 

•        Kidney problems

•        Antibiotic-associated Diarrhea –watery diarrhea

                                                    Blood in your stool 

                                                    Severe stomach cramps

OVERDOSE:

Symptoms of overdose include

•        Confusion

•        Drowsiness

•        Blurred vision

•        Fast or pounding heartbeat

•        Nausea

•        Vomiting

•        Sweating

•        Headache

TOXICITY:

Overdose of omeprazole can lead to toxicity. Overdose of omeprazole up to 2400 mg has been reported. Dialysis may not be helpful as omeprazole is extensively protein-bound. Symptomatic and supportive care is recommended with an overdose.

STORAGE:

Maintain temperature between 68°F and 77°F (20°C and 25°C).