Ranitidine and H2-antagonists

Very recently, a very bold chemical model for histamine H2-receptors has been proposed using [18]aneN6-3H+ 84), which can chemically recognize histamine, histamine H2-agonists, and histamine H2-antagonists such as cimetidine XII or ranitidine XIII that are currently in world-wide use for treatment of peptic ulcers 85). 

These drug inhibit die action of histamine at histamine H2 receptor cells of die stomach, which then reduces die secretion of gastric acid and reduces total pepsin output. The decrease in acid allows the ulcerated areas to heal. Examples of histamine H2 antagonists include cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid Pulvules), ranitidine (Zantac). 

HISTAMINE H2 ANTAGONISTS. The nurse administers ranitidine and oral cimetidine before or with meals and at bedtime Nizatidine and famotidine are given at bedtime or, if twice-a-day dosing is prescribed, in the morning and at bedtime. These drugp are usually given concurrently with an antacid to relieve the pain. In certain situations or disorders, cimetidine and ranitidine may also be given by intermittent IV infusion or direct IV injection. 

The following amides prepared from 4-(3-nitro-l-pyrazolyl)butanoic acid, CDI, and primary amines represent partial structures of the histamine H2-receptor antagonists roxatidine, cimetidine, ranitidine, and famotidine [37]... 

Lee, K. and D. R. Thakker. Saturable transport of H2-antagonists ranitidine and famotidine across Caco-2 cell monolayers, J. Pharm. Sci. 1999, 88, 680-687... 

If 10% of patients previously receiving prescriptions for an antacid were prescribed a H2 antagonist such as cimetidine or ranitidine, this claimed savings would not have been achieved. The growth in the H2 antagonist market was rapid at this time, and some of this growth must have been due to such escalation of prescribing. 

Histamine H2-receptor antagonists are well absorbed orally, although concurrent antacid therapy may reduce bioavailability by up to 30%. They are widely distributed in the body, crossing the blood-brain barrier and the placenta. Cimetidine, ranitidine and famotidine are extensively metabolised in the liver, and about one-third excreted unchanged in urine, while only one-third of nizatidine is metabolised (Table 11.1). Elimination half-life is increased up to tenfold in renal failure, and doses must be adjusted. 

Histamine H2-receptor antagonists are the mainstay of prevention of Mendelson s syndrome at present. Probably the best protection is afforded by a combination of H2-receptor blockade by ranitidine and a single oral dose of sodium citrate or bicarbonate. Because of its longer duration of action, and relative lack of enzyme inhibition, ranitidine is preferred to cimetidine for this purpose, although there is a latent period of 1-2 hours before it takes effect. Famotidine and nizatidine are probably equally effective in blocking acid secretion. 

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