H2-receptor antagonists
H2-receptor antagonists
H2-receptor antagonists are commonly prescribed antiulcer drugs in the United States. They include:
- cimetidine
- famotidine
- nizatidine
- ranitidine.
Pharmacokinetics
Cimetidine, nizatidine, and ranitidine are absorbed rapidly and completely from the GI tract. Famotidine isn’t completely absorbed. Antacids may reduce the absorption of H2-receptor antagonists.
Distribution, metabolism, and excretion
H2-receptor antagonists are distributed widely throughout the body, metabolized by the liver, and excreted primarily in urine.
Pharmacodynamics
H2-receptor antagonists block histamine from stimulating the acid-secreting parietal cells of the stomach.
The acid test
Acid secretion in the stomach depends on the binding of gastrin, acetylcholine, and histamine to receptors on the parietal cells. If the binding of one of these substances is blocked, acid secretion is reduced. The H2-receptor antagonists, by binding with H2 receptors, block the action of histamine in the stomach and reduce acid secretion.
Pharmacotherapeutics
H2-receptor antagonists are used therapeutically to:
- promote healing of duodenal and gastric ulcers
- provide long-term treatment of pathologic GI hypersecretory conditions such as Zollinger-Ellison syndrome
- reduce gastric acid production and prevent stress ulcers in the severely ill patient and in the patient with reflux esophagitis or upper GI bleeding.
Drug interactions
H2-receptor antagonists may interact with antacids and other drugs.
Now I get it!
How H2-receptor antagonists work
These illustrations show how histamine-2 (H2) receptor antagonists reduce the release of gastric acid.
To stimulate gastric acid secretion, certain endogenous substances’primarily histamine, but also acetylcholine and gastrin’attach to receptors on the surface of parietal cells. These substances activate the enzyme adenyl cyclase, which converts adenosine triphosphate (ATP) to the intracellular catalyst cyclic adenosine monophosphate (cAMP).
The cAMP ultimately stimulates proton-pump (H/K ATPase) activity. The pump catalyzes the exchange of extracellular potassium (K) ions for intracellular hydrogen (H) ions. When the H+ ions combine with extracellular chloride (Cl) ions excreted by gastric cells at a different site, the result is hydrochloric (HCl), or gastric, acid.
H2-receptor antagonists competitively bind to H2-receptor sites on the surface of parietal cells and inhibit the common pathway that histamine and the other substances must travel to stimulate proton-pump activity and promote gastric acid secretion.
- Antacids reduce the absorption of cimetidine, famotidine, nizatidine, and ranitidine.
- Cimetidine may increase the blood levels of oral anticoagulants, propranolol (and possibly other beta-adrenergic blockers), benzodiazepines, tricyclic antidepressants, theophylline, procainamide, quinidine, lidocaine, phenytoin, calcium channel blockers, cyclo-sporine, carbamazepine, and opioid analgesics by reducing their metabolism in the liver and subsequent excretion.
- Cimetidine taken with carmustine increases the risk of bone marrow toxicity.
- Cimetidine inhibits metabolism of ethyl alcohol in the stomach, resulting in higher blood alcohol levels.
Warning!
Adverse reactions to H2-receptor antagonists
The use of H2-receptor antagonists may lead to adverse reactions, especially in the elderly patient and the patient with altered hepatic or renal function.
- Cimetidine and ranitidine may produce headache, dizziness, malaise, muscle pain, nausea, diarrhea or constipation, rash, itching, loss of sexual desire, gynecomastia (cimetidine), and impotence.
- Famotidine and nizatidine produce few adverse reactions; head-ache is the most common, followed by constipation or diarrhea and rash
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