| Indication |
Used in the treatment of peptic ulcer disease (PUD), dyspepsia,
stress ulcer prophylaxis, and gastroesophageal reflux disease (GERD). |
| Pharmacodynamics |
Ranitidine is a histamine H2-receptor antagonist similar to
cimetidine and famotidine. An H2-receptor antagonist, often shortened to
H2 antagonist, is a drug used to block the action of histamine on
parietal cells in the stomach, decreasing acid production by these
cells. These drugs are used in the treatment of dyspepsia, however their
use has waned since the advent of the more effective proton pump
inhibitors. Like the H1-antihistamines, the H2 antagonists are inverse
agonists rather than true receptor antagonists. |
| Mechanism of action |
The H2 antagonists are competitive inhibitors of histamine at the
parietal cell H2 receptor. They suppress the normal secretion of acid by
parietal cells and the meal-stimulated secretion of acid. They
accomplish this by two mechanisms: histamine released by ECL cells in
the stomach is blocked from binding on parietal cell H2 receptors which
stimulate acid secretion, and other substances that promote acid
secretion (such as gastrin and acetylcholine) have a reduced effect on
parietal cells when the H2 receptors are blocked. |
| Absorption |
Approximately 50% bioavailability orally. |
| Volume of distribution |
- 1.4 L/kg
- 1.76 L/kg [clinically significant renal function impairment (creatinine clearance 25 to 35 mL/min)]
|
| Protein binding |
15% |
| Metabolism |
Hepatic. Ranitidine is metabolized to the N-oxide, S-oxide, and
N-desmethyl metabolites, accounting for approximately 4%, 1%, and 1% of
the dose, respectively. |
| Route of elimination |
The principal route of excretion is the urine (active tubular
excretion, renal clearance 410mL/min), with approximately 30% of the
orally administered dose collected in the urine as unchanged drug in 24
hours. |
| Half life |
2.8-3.1 hours |
| Clearance |
- 29 mL/min [clinically significant renal function impairment]
- 3 mL/min/Kg [neonatal patients]
|
| Toxicity |
LD50=77mg/kg (orally in mice). Symptoms of overdose include muscular tremors, vomiting, and rapid respiration. |
