PHARMACOLOGY

H2 RECEPTOR PHARMACOLOGICAL ACTIONS ::

     H2 receptor antagonists inhibit basal and meal stimulated gastric acid secretion in normal and patients suffering from peptic or duodenal ulcers Nocturnal gastric acid output is decreased by 80-90% The inhibition of secretion is due to competitive antagonism at H2 receptors Acetylcholine induced gastric acid secretion is also decreased by these agents it is proposed that there are both cholinergic and histaminergic nerves The stimulation of the cholinergic nerve leads to stimulation of histamine fibres or release of histamine in the gastric mucosa The released histamine finally stimulates H2 receptors to initiate gastric acid secretion 

Pharmacokinetics ::

All histamine H2 receptor antagonists are absorbed orally well The oral bioavailability of nizatidine is appoximately 90% whereas that of others is limited to 50% because of first pass metabolism Peak effect is reached within 2 hrs Half life of ranitidine is higher in patients with hepatic dysfunction They are excreted unchanged in kidney by tubular secretion 

Therapeutic Ulcers ::

(1) Peptic Ulcers (2) Duodenal Ulcers and (3) Zolliger Ellison Syndrome Their therapeutic use is extended to gastritis esophagitis heart burn etc 

    Ranitidine is 5 to 10 times more potent than cimetidine Ranitidine is given in the dose of 150 mg and cimetidine in 400 mg 600 mg two to four times a day After oral administration peak effect is reached in 60-90 min Major portion of these agents is excreted in urine 

Adverse effects ::

Cimetidine may cause skin rash headache dizziness gyneomastia impotence mental confusion lethargy and hepatotoxicity Cimeidine also inhibits hepatic microsomal enzymes and interferes with metabolism of warfarin phenytoin propranolol diazepam and theophylline 

    Ranitidine is well tolerated and devoid of adverse effects produced by cimetidine Ranitidine does not cross BBB and hence does not cause hypergalactemia or gynecomastia it does not bind with cytochrome P450