what is H2 blockers?
what is H2 blockers?
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A chemical called histamine stimulates cells in the stomach lining to make hydrochloric acid. Too much of this acid can cause GERD and other painful conditions.
H2 blockers bind to histamine receptors in the stomach, reducing the amount of acid that the stomach lining secretes. This helps relieve symptoms of an overproduction of stomach acid.This type of drug usually offers relief within 60 minutesTrusted Source, and the effects can last 4–10 hours.
H2 blockers can treat or prevent a number of health problems, including:
-heartburn
-GERD
-duodenal and gastric ulcers
-upper gastrointestinal bleeding
-gastric hypersecretory diseases, such as Zollinger-Ellison syndrome
Mechanism of Action
Mechanism of Action
H2RAs decrease gastric acid secretion by reversibly binding to histamine H2 receptors located on gastric parietal cells, thereby inhibiting the binding and activity of the endogenous ligand histamine. H2 blockers thus function as competitive antagonists. Normally, after a meal, gastrin stimulates histamine release from enterochromaffin-like cells, which then binds to histamine H2 receptors on gastric parietal cells and leads to gastric acid release. This increase in gastric acid release occurs through the activation of adenylate cyclase, which raises intracellular cAMP levels. cAMP then activates protein kinase A (PKA), which, among other functions, phosphorylates proteins involved in the movement of H+/K+ ATPase transporters to the plasma membrane. The increase of H+/K+ ATPase transporters at the plasma membrane allows for the secretion of more acid from parietal cells. By blocking the histamine receptor and thus histamine stimulation of parietal cell acid secretion, H2RAs suppress both stimulated and basal gastric acid secretion induced by histamine.[6] The onset of gastric relief provided by H2RAs is approximately 60 minutes with a duration of action that ranges from 4 to 10 hours, making them useful for the on-demand treatment of occasional symptoms. All H2RAs have similar efficacy in decreasing gastric acid secretion.
H2RAs decrease gastric acid secretion by reversibly binding to histamine H2 receptors located on gastric parietal cells, thereby inhibiting the binding and activity of the endogenous ligand histamine. H2 blockers thus function as competitive antagonists. Normally, after a meal, gastrin stimulates histamine release from enterochromaffin-like cells, which then binds to histamine H2 receptors on gastric parietal cells and leads to gastric acid release. This increase in gastric acid release occurs through the activation of adenylate cyclase, which raises intracellular cAMP levels. cAMP then activates protein kinase A (PKA), which, among other functions, phosphorylates proteins involved in the movement of H+/K+ ATPase transporters to the plasma membrane. The increase of H+/K+ ATPase transporters at the plasma membrane allows for the secretion of more acid from parietal cells. By blocking the histamine receptor and thus histamine stimulation of parietal cell acid secretion, H2RAs suppress both stimulated and basal gastric acid secretion induced by histamine.[6] The onset of gastric relief provided by H2RAs is approximately 60 minutes with a duration of action that ranges from 4 to 10 hours, making them useful for the on-demand treatment of occasional symptoms. All H2RAs have similar efficacy in decreasing gastric acid secretion.
Adverse Effects
H2 receptor antagonists are generally well-tolerated. Mild side effects may include headache, drowsiness, fatigue, abdominal pain, constipation, or diarrhea. The use of H2RAs in patients with renal impairment, hepatic impairment, or who are over 50 years of age has correlated with central nervous system side effects such as delirium, confusion, hallucinations, or slurred speech. Cimetidine is generally considered the most frequent cause of these symptoms, although similar effects have also occurred with famotidine.
Drug interactions with H2 receptor antagonists may occur. As a result of the therapeutic increase in gastric pH, the absorption of drugs requiring an acidic environment for dissolution may become altered. Cimetidine is a potent cytochrome P450 (CYP450) enzyme inhibitor and should be avoided with other medications metabolized by CYP450 enzymes such as theophylline, selective serotonin reuptake inhibitors, or warfarin. Prolonged, high doses of cimetidine have also been linked to gynecomastia, reduced sperm count, and impotence in men and galactorrhea in women. This condition typically resolves with drug discontinuation. Today, clinicians generally avoid cimetidine as a therapeutic recommendation for gastric symptoms.
Using H2 receptor antagonists on a scheduled basis may result in tachyphylaxis or tolerance, limiting their use as maintenance therapy for GERD symptoms. Tolerance to the effects of H2RAs can occur within 7 to 14 days of continued treatment. Intermittent, or as needed, H2RAs may help prevent the development of tachyphylaxis.
Compared to proton pump inhibitors, H2RAs pose a minor risk for developing bacterial overgrowth and infections.
Administration
Administration
H2 receptor antagonists are well-absorbed after oral administration, and all H2RAs are available as a tablet for oral use. Nizatidine is also available as a capsule or an oral solution. Famotidine, one of the most commonly used agents, is available as a chewable tablet, oral powder for suspension, or in combination formulations containing calcium carbonate and magnesium hydroxide or ibuprofen. Of the H2RAs, famotidine is available as an intravenous solution for use in hospital settings.
H2 receptor antagonists may be used as needed for gastric symptom relief or prophylactically 30 to 60 minutes before known food or beverage triggers. H2RAs may also be taken concomitantly with antacids if both quick relief of symptoms and a longer duration of action are desired. For best results, patients should take once-daily doses of H2RAs at bedtime. The more common twice-daily doses can be taken once in the morning and once in the evening. Patients should not initially self-treat with H2RAs for longer than two weeks without consulting their primary care physician.
Contraindications
There are currently no absolute contraindications to H2RAs. However, they should not be used in patients with known hypersensitivity to any H2RA or other drug components. Patients should stop using OTC H2RAs if they are experiencing trouble or pain when swallowing food, vomiting with blood, or experiencing bloody or black stools. Instead, they should seek appropriate medical attention.
Toxicity
H2 receptor antagonists have a broad therapeutic index and, therefore, severe toxicity is rare. Toxicities of H2RAs may be associated with inhibition of H2 receptors in the myocardium and central nervous system. Central nervous system depression, hypotension, and bradycardia have rarely been reported and usually involve the rapid intravenous infusion of an H2RA. Treatment for toxicities related to H2RA use may include decontamination with gastric lavage or activated charcoal, discontinuation of the drug, and supportive care measures.
nizatidine-1.docxfamotidine-1.docxMADE BY: NOHA SAMY MOHAMMED HELAL
NERMEEN AHMED HEDIA
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