Proton Pump Inhibitors

Definition
Purpose
Description
Recommended dosage
Precautions
Side effects
Interactions

Definition

The proton pump inhibitors are a group of drugs that reduce the secretion of gastric (stomach) acid. They act by binding with the enzyme H+, K(+)-ATPase, hydrogen/potassium adenosine triphosphatase, which is sometimes referred to as the proton pump. This enzyme causes parietal cells of the stomach lining to produce acid.

Although they perform much the same functions as the histamine H-2 receptor blockers, the proton pump inhibitors reduce stomach acid more and over a longer period.

Purpose

Proton pump inhibitors are used to treat ulcers; gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and injury of the food pipe (esophagus); and conditions in which the stomach produces too much acid, such as Zollinger-Ellison syndrome. Omeprazole is used in combination with other medications to treat recurrent ulcers caused by helicobacter pylori infections.

Two of the proton pump inhibitors, lansoprazole and omeprazole, have been used to improve pancreatic enzyme absorption in cystic fibrosis patients with intestinal malabsorption.

Proton pump inhibitors may be used to protect against the ulcerogenic effects of non-steroidal anti-inflammatory drugs and to help heal ulcers caused by these drugs.

Description

There are five drugs in this class: esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), and rabeprazole (Aci-pHex). They act in a similar manner, and their cautions and adverse effects are similar.

The products are generally formulated as enteric-coated granules. Absorption does not start until the granules have left the stomach and reached the intestine, so the onset of action is delayed about an hour, subject to gastric emptying time. Since they act slowly, proton pump inhibitors are not a suitable alternative to antacids which have a rapid effect.

Although these drugs are eliminated from the body relatively quickly, usually within 90 minutes of absorption, they all work for over 24 hours after a dose. This is because the factor that determines duration of action is how long it takes the body to replace the H +, K( +)-ATPase. There is some build up over time. For example, a single dose of lansoprazole reduces stomach acid by 71%, but after a week of regular dosing, the acid reduction rises to 80%.

For treatment of recurrent ulcers, the proton pump inhibitors are part of combination therapy that uses an antibiotic (occasionally two antibiotics ) and proton pump inhibitor. There are a number of regimens, and while they may vary in the selection of specific drugs, or even types of drugs used, usually they include a proton pump inhibitor. The cure rates are all within similar ranges for these regimens.

Recommended dosage

Dose varies with the indication. The following are commonly prescribed doses:

• Esomeprazole: 20 to 40 mg once a day.
• Lansoprazole: 15 to 30 mg once a day.
• Omeprazole: 20 to 40 mg once a day.
• Pantoprazole: 40 mg once or twice a day.
• Rabeprazole: 20 mg once a day. In hypersecretory conditions, doses as high as 60 mg twice daily have been reported.

In the above examples, the lower dose is usually adequate for GERD, while the higher dose may be required for ulcer therapy or hypersecretory conditions.

Precautions

Proton pump inhibitors should not be given to any patient who has shown a reaction to any of the components of the drug or a related drug. Proton pump inhibitors should also not be given to patients with severe liver disease.

Omeprazole is pregnancy category C, while esomeprazole, lansoprazole, rabeprazole, and pantoprazole are category B. As of 2008, there are no adequate and well-controlled studies concerning the effects of these drugs on pregnant women. These drugs should be used during pregnancy only if the potential benefit justifies the risk to the fetus. Because the proton pump inhibitors are excreted into breast milk, they should not be used by women who are breastfeeding their babies.

The proton pump inhibitors may mask the symptoms of stomach cancer.

Side effects

The proton pump inhibitors are relatively safe drugs. The most commonly observed adverse effects are constipation, diarrhea, dizziness, headache, skin itch, and skin rash. Less often, the following adverse effects have been reported: abdominal pain with cramps, appetite changes, and nausea.

The following adverse effects are extremely rare but have been reported with this class of drugs:

• acute pancreatitis
• anxiety
• cough
• depression
• drug toxin-related hepatitis
• erythema multiforme

KEY TERMS

Antacid— A substance that counteracts or neutralizes acidity, usually of the stomach. Antacids have a rapid onset of action compared to histamine H-2 receptor blockers and proton pump inhibitors, but they have a short duration of action and require frequent dosing.

Cystic fibrosis— A hereditary disease that appears in early childhood, involves functional disorder of digestive glands, and is marked especially by faulty digestion due to a deficiency of pancreatic enzymes, by difficulty in breathing due to mucus accumulation in airways, and by excessive loss of salt in the sweat.

Enteric coat— A coating put on some tablets or capsules to prevent their disintegration in the stomach. The contents of coated tablets or capsules will be released only when the dose reaches the intestine. This may be done to protect the drug from stomach acid, to protect the stomach from drug irritation, or to delay the onset of action of the drug.

GERD— A chronic condition in which the lower esophageal sphincter allows gastric acids to reflux into the esophagus, causing heartburn, acid indigestion, and possible injury to the esophageal lining.

Malabsorption— Defective or inadequate absorption of nutrients from the intestinal tract.

Parietal cells— Cells of the gastric glands that secret hydrochloric acid.

Recurrent ulcer— Stomach ulcers that return after apparently complete healing. These ulcers appear to be caused by helicobacter pylori infections and can generally be successfully treated with a combination of antibiotics and gastric acid reducing compounds, particularly the proton pump inhibitors.

• flu-like symptoms
• myalgia
• Stevens-Johnson syndrome
• thrombocytopenia
• toxic epidermal necrolysis
• ulcerative colitis
• upper respiratory hypersensitivity reaction
• upper respiratory infection
• vomiting

Interactions

Proton pump inhibitors should not be used in conjunctions with the anti-retroviral (anti-AIDS) drug atazanavir (Rayataz). The conjunction may reduce the effectiveness of the atazanavir. Proton pump inhibitors should not be used in combination with the anti-fungal drugs itraconazole or ketoconazole. This combination may reduce the effectiveness of the anti-fungal drugs.

Resources

BOOKS

Atkinson, A. J., D. R. Abernathy, C. E. Daniels, R. Dedrick, and S. P. Markey. Basic & Clinical Pharmacology. 2nd ed. New York: Academic Press, 2006.

Edmunds, M. W. Introduction to Clinical Pharmacology. 5th ed St. Louis: Mosby, 2005.

Katzung, B. G. Basic & Clinical Pharmacology. 10th ed. New York: McGraw-Hill, 2006.

Roach, S., S., and S. M. Ford. Introductory Clinical Pharmacology. 8th ed. Philadelphia: Lippincott Williams & Wilkins, 2006.

PERIODICALS

Dharmarajan, T. S., M. R. Kanagala, P. Murakonda, A. S. Lebelt, and E. P. Norkus. “Do Acid-lowering agents affect vitamin B12 status in older adults?.” Journal of the American Medical Directors Association 9, no. 3 (2008): 162–167.

Freeman, H. J. “Proton pump inhibitors and an emerging epidemic of gastric fundic gland polyposis.” World Journal of Gastroenterology 14, no. 9 (2008): 1318–1320.

Sheiman, J. M. “Prevention of NSAID-Induced Ulcers.” Current Treatment Options in Gastroenterology 11, no. 2 (2008): 125–134.

Wright, M. J., D. D. Proctor, K. L. Insogna, and J. E. Kerstetter. “Proton pump-inhibiting drugs, calcium homeostasis, and bone health.” Nutrition Review 66, no. 2 (2008): 103–108.

ORGANIZATIONS

American College of Clinical Pharmacy. http://www.accp.com/.

American College of Clinical Pharmacology. http://www.accpl.org.

American College of Physicians. 190 N Independence Mall West, Philadelphia, PA 19106-1572. (800) 523-1546, x2600, or (215) 351-2600. http://www.acponline.org.

American Medical Association. 515 N. State Street, Chicago, IL 60610. (312) 464-5000. http://www.ama-assn.org.

OTHER

Drug Information Association. Information about prescription drugs. 2008 [cited February 25, 2008]. http://www.diahome.org/DIAHome/.

Mayo Clinic. Information about prescription drugs. 2008[cited February 24, 2008]. http://www.mayoclinic.com/health/drug-information/DrugHerbIndex.

National Library of Medicine. Information about prescription drugs. 2008 [cited February 24, 2008]. http://www.nlm.nih.gov/medlineplus/druginformation.html/.

Physician’s Drug Reference. Information about prescription drugs. 2008 [cited February 22, 2008]. http://www.pdr.net/drug-information/?engin=adwords!8815&keyword=%2Adrug+information%2A&match_type=&gclid=CMztjYHjgJICFQrAaAodKE3

L. Fleming Fallon, Jr, MD, DrPH

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