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| human digestive system |
Proton pump inhibitors reduce the production of acid by blocking the enzyme in the wall of the stomach that produces acid. The reduction of acid prevents ulcers and allows any ulcers that exist in the esophagus, stomach, and duodenum to heal.
Classification of PPIs:
Proton pump inhibitors are very similar in action and there is no evidence that one is more effective than another. They differ in how they are broken-down by the liver and their drug interactions. The effects of some PPIs may last longer and they, therefore, may be taken less frequently.
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| Omeprazole |
- Omeprazole,
- Lansoprazole,
- Dexlansoprazole,
- Esomeprazole,
- Pantoprazole,
- Rabeprazole.
Proton Pump Inhibitors (PPIs) uses:
Proton pump inhibitors are used for the prevention and treatment of acid-related conditions such as:- ulcers,
- gastroesophageal reflux disease (GERD), and
- Zollinger-Ellison syndrome.
They also are used in combination with antibiotics for eradicating Helicobacter pylori, a bacterium that together with acid causes ulcers of the stomach and duodenum.
Side-effects of PPIs:
The most common side effects of proton pump inhibitors are:- headache,
- diarrhea,
- constipation,
- abdominal pain,
- nausea, and
- rash.
Nevertheless, proton pump inhibitors generally are well tolerated.
High doses and long-term use (1 year or longer) may increase the risk of osteoporosis-related fractures of the hip, wrist, or spine. Therefore, it is important to use the lowest doses and shortest duration of treatment necessary for the condition being treated.
PPIs interaction with other drugs:
Proton pump inhibitors interact with few drugs. The absorption into the body of some drugs is affected by the presence of acid in the stomach, and because PPIs reduce acid in the stomach, they may affect the absorption of these drugs. Specifically, PPIs reduce the absorption and concentration in the blood of ketoconazole (Nizoral) and increase the absorption and concentration of digoxin (Lanoxin). This may lead to reduced effectiveness of ketoconazole and an increase in digoxin toxicity.
Mechanisms Of Action:
Proton pump inhibitors(PPI) act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase, or more commonly just gastric proton pump) of the gastric parietal cell. The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion. (“Irreversibility” refers to the effect on a single copy of the enzyme; the effect on the overall human digestive system is reversible, as the enzymes are naturally destroyed and replaced with new copies.)
Targeting the terminal-step in acid production, as well as the irreversible nature of the inhibition, result in a class of drugs that are significantly more effective than H2 antagonists and reduce gastric acid secretion by up to 99%.
The lack of the acid in the stomach will aid in the healing of duodenal ulcers, and reduces the pain from indigestion and heartburn, which can be exacerbated by stomach acid. However, lack of stomach acid is also called hypochlorhydria, the lack of sufficient hydrochloric acid, or HCl. Hydrochloric acid is required for the digestion of proteins and for the absorption of nutrients, particularly of vitamin B12 and of calcium.
The proton pump inhibitors are given in an inactive form. The inactive form is neutrally charged (lipophilic) and readily crosses cell membranes into intracellular compartments (like the parietal cell canaliculus) that have acidic environments. In an acid environment, the inactive drug is protonated and rearranges into its active form. As described above, the active form will covalently and irreversibly bind to the gastric proton pump, deactivating it.
