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Mechanism of action and pharmacological effect - Proton inhibitors:
(1) Acts as a pro-drug and must be activated by exposure to acidic pH (< 5).

(2) The activated species irreversibly binds to the H+, K+ - ATPase enzyme (proton pump) in the parietal cell apical membrane inhibiting it’s activity. New enzyme has to be synthesized to overcome the inhibition.

(3) Has little effect on gastric acid volume and does not affect gastric motility.

(4) Effective in decreasing gastric acid production by more than 95%.

 dexlansoprazole -dexilant®

DEXILANT is a proton pump inhibitor (PPI) indicated for:
Healing of all grades of erosive esophagitis (EE).
Maintaining healing of EE and relief of heartburn.
Treating heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (GERD).

Healing of EE: 60 mg once daily for up to 8 weeks.
Maintenance of healed EE: 30 mg once daily for up to 6 months.
Symptomatic non-erosive GERD: 30 mg once daily for 4 weeks.

Hepatic impairment: Consider 30 mg maximum daily dose for patients with moderate hepatic impairment (Child-Pugh Class B). No studies were conducted in patients with severe hepatic impairment (Child-Pugh Class C).

DEXILANT can be taken without regard to food.  DEXILANT should be swallowed whole. Alternatively, capsules can be opened, sprinkled on one tablespoon of applesauce, and swallowed immediately.

Delayed-Release Capsules: 30 mg and 60 mg.

Esomeprazole (nexium ®) 

Healing of Erosive Esophagitis: 20 - 40 mg once daily x 4 to 8 weeks. May consider an additional 4-8 weeks of treatment if patient is not healed.

Maintenance of Healing of Erosive Esophagitis: 20 mg once daily.

Symptomatic Gastroesophageal Reflux Disease: 20 mg once daily x 4 weeks. May consider an additional 4 weeks of treatment if symptoms do not resolve.

Treatment of GERD (short-term): 20 mg or 40 mg IV once daily for </= 10 days. Change to oral therapy as soon as appropriate.

H. pylori Eradication (Triple therapy): Nexium 40 mg qd x 10 days + Amoxicillin 1000 mg bid x 10 Days + Clarithromycin 500 mg bid for 10 days.

[Supplied: 20, 40mg capsules. Injection (powder for reconstitution) 20 mg, 40 mg]

Drug update - new formulation
ESOMEPRAZOLE STRONTIUM delayed-release capsules for oral use
[Drug information  /  PDF]  
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2013

Mechanism of Action: Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. The S- and R-isomers of omeprazole are protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. By acting specifically on the proton pump, esomeprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-related up to a daily dose of 20 to 40 mg and leads to inhibition of gastric acid secretion.

Esomeprazole strontium is a proton pump inhibitor indicated for adults for:
Treatment of gastroesophageal reflux disease (GERD) (1.1)
Risk reduction of NSAID-associated gastric ulcer (1.2)
H. pylori eradication to reduce the risk of duodenal ulcer recurrence (1.3)
Pathological hypersecretory conditions, including Zollinger-Ellison syndrome (1.4)

Delayed-Release Capsules
24.65 mg of esomeprazole strontium (equivalent to 20 mg of esomeprazole)
49.3 mg of esomeprazole strontium (equivalent to 40 mg of esomeprazole)

Lansoprazole  (prevacid ® )

GERD: 15-30mg orally once daily before meal.

Hypersecretory: Maximum: 180mg/day. Duodenal ulcer: 15 mg orally once daily x 4 weeks. Maintenance therapy: 15 mg once daily. Gastric ulcer: 30 mg orally once daily for up to 8 weeks.
Erosive esophagitis:
-Short-term treatment: 30 mg orally once daily for up to 8 weeks. Continued treatment for an additional 8 weeks may be considered for recurrence or for patients that do not heal after the first 8 weeks of therapy.
-Maintenance therapy: 15 mg once daily. Alternatively: 30 mg IV once daily for up to 7 days. Patients should be switched to an oral formulation as soon as they can take oral medications.

Hypersecretory conditions: Initially 60 mg orally once daily. Adjust dose based upon patient response and to reduce acid secretion to <10 mEq/hour (5 mEq/hour in patients with prior gastric surgery). Doses of 90 mg twice daily have been used. Administer doses >120 mg/day in divided doses

Prevention of rebleeding in peptic ulcer bleed (unlabeled use): 60 mg IV, followed by 6 mg/hour infusion for 72 hours.

Supplied: delayed release capsule: 15 mg, 30 mg. Oral suspension: 15 mg/packet, 30 mg/packet. Injection (powder for reconstitution): 30 mg. Orally-disintegrating tablet: 15 mg, 30 mg.

Omeprazole (prilosec ® )

Usual: 20-40mg orally once daily.
Hypersecretory: 60mg once daily.

Active bleeding (IV formulation of PPI not available): 40 mg po bid. If there is no rebleeding within 24 hours, the patient may be switched to oral omeprazole 20 mg/day.

YOSPRALA™ (aspirin and omeprazole)

Pantoprazole  (protonix ® )

Adult (usual):
Short-term treatment erosive esophagitis: 40 mg orally once daily for 8-16 weeks. Alternatively, 40 mg IV once daily infusion for 7-10 days.
Gastroesophageal reflux disease (maintain healing erosive esophagitis): 40 mg orally once daily.

Hypersecretory conditions: 80 mg IV infusion every 12 hours. Can increase to every 8 hours - Max: 240 mg/day. Alternatively: 40 mg orally twice daily. Max: 240 mg/day. Peptic ulcer: 40-80 mg orally once daily x 4-8 weeks.

Prevention of rebleeding in peptic ulcer bleed (unlabeled use): 80 mg IV, followed by 8 mg/hour infusion for 72 hours

[Supplied: Enteric coated tablet: 20, 40mg. Lyophilized powder: 40mg vial.]

Rabeprazole sodium (aciphex ®)

Adult ((usual):  20 mg once daily. The recommended starting oral dose for the treatment of hypersecretory conditions is 60mg once daily (may increase up to 120 mg). Give on empty stomach before meals. Do not chew or crush.

[Supplied: 20mg tab]

 zegerid® (omeprazole, sodium bicarbonate) 

ZEGERID is a proton pump inhibitor indicated for:
Short-term treatment of active duodenal ulcer
Short-term treatment of active benign gastric ulcer
Treatment of gastroesophageal reflux disease (GERD)
Maintenance of healing of erosive esophagitis
Reduction of risk of upper GI bleeding in critically ill patients

The safety and effectiveness of ZEGERID in pediatric patients (<18 years of age) have not been established.

Short-Term Treatment of Active Duodenal Ulcer: 20 mg once daily for 4 weeks (some patients may require an additional 4 weeks of therapy (14.1))
Gastric Ulcer: 40 mg once daily for 4-8 weeks
Gastroesophageal Reflux Disease (GERD)

-Symptomatic GERD (with no esophageal erosions): 20 mg once daily for up to 4 weeks
-Erosive Esophagitis: 20 mg once daily for 4-8 weeks

Maintenance of Healing of Erosive Esophagitis: 20 mg once daily.
Reduction of Risk of Upper Gastrointestinal Bleeding in Critically Ill Patients: (40mg oral suspension only) 40 mg initially followed by 40 mg 6-8 hours later and 40 mg daily thereafter for 14 days.

ZEGERID is available as a capsule and as a powder for oral suspension in 20 mg and 40 mg strengths

Treatment of bleeding peptic ulcers 

Considering the available data, the ideal pharmacologic therapy for patients with acute ulcer bleeding appears to be an intravenous proton pump inhibitor started immediately after endoscopic therapy. Although omeprazole has been the most extensively studied, other intravenous formulations of proton pump inhibitors given in doses that are known to inhibit gastric acid secretion are probably acceptable alternatives. Pantoprazole and lansoprazole and esomeprazole are the only intravenous formulations available in the United States. The suggested IV pantoprazole dose is 80 mg bolus followed by 8 mg/hr infusion. If there is no rebleeding within 24 hours, the patient may be switched to oral pantoprazole 40 mg/day or omeprazole 20 mg/day.

Oral dosing: Twice daily dosing (high dose) of an oral proton pump inhibitor may be a reasonable alternative if intravenous formulations are not available. While data are limited, oral administration of a proton pump inhibitor using standard doses in the acute bleeding setting may not affect bleeding risk since it may take several days to achieve adequate acid suppression. One of the largest and most rigorously conducted controlled trials conducted in India found that a high dose of oral omeprazole (40 mg PO BID) was associated with a decreased risk of recurrent bleeding in patients who had ulcers with a visible vessel or adherent clots who did not undergo endoscopic therapy. This study suggests that the theoretical limitation of oral dosing may in part be overcome by using high doses given twice daily. Another controlled trial involving patients at high risk for rebleeding suggested that patients treated with injection therapy may also benefit from oral omeprazole.

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Proton pump inhibitors