indication

Used in the treatment of peptic ulcer disease (PUD), dyspepsia, stress ulcer prophylaxis, and gastroesophageal reflux disease (GERD).

pharmacology

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.

toxicity

LD₅₀=77mg/kg (orally in mice). Symptoms of overdose include muscular tremors, vomiting, and rapid respiration.

biotransformation

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.

absorption

Approximately 50% bioavailability orally.

half life

2.8-3.1 hours

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.

drug interactions

Acenocoumarol: Ranitidine may increase the anticoagulant effect of acenocoumarol. (Conflicting evidence)

Anisindione: Ranitidine may increase the anticoagulant effect of anisindione. (Conflicting evidence)

Atazanavir: Ranitidine may decrease the levels/effects of atazanavir.

Cefditoren: H2-Antagonists such as ranitidine may decrease the serum concentration of cefditoren. Cefditoren prescribing information recommends to avoid concomitant use with H2-antagonists (eg, famotidine, ranitidine) and antacids as well. Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of H2-antagonists can not be avoided.

Dasatinib: Ranitidine may decrease the serum level of dasatinib.

Dicumarol: Ranitidine may increase the anticoagulant effect of dicumarol. (Conflicting evidence)

Itraconazole: The H2-receptor antagonist, ranitidine, may decrease the absorption of itraconazole.

Ketoconazole: The H2-receptor antagonist, ranitidine, may decrease the absorption of ketoconazole.

Procainamide: The histamine H2-receptor antagonist, ranitidine, may increase the effect of procainamide.

Tolazoline: Anticipated loss of efficacy of tolazoline

Warfarin: Ranitidine may increase the anticoagulant effect of warfarin. (Conflicting evidence)