H2 Receptor Antagonists
receptor antagonists competitively inhibit the interaction of histamine with H2
receptors. They are highly selective and have little or minimal effect on H1
or other recep-tors. H2 antagonists
mainly interfere with gastric secretion, although they exert inhibitory effects
on cardiovascular and other systems affected by H2
receptors. They do not exhibitanticholinergic properties.
examples of this group of drugs used widely in the treatment of peptic and
duodenal ulcer, include cimetidine, ranitidine, famotidine, nizatidine and
has been implicated in causing significant drug interactions with a number of
other therapeutic drugs because of its ability to inhibit cytochrome P450 mixed
function oxidase activity— amitryptiline, benzodiazepines, carbamazepine,
imipramine, lignocaine, nifedipine, phenytoin, quinidine, terfenadine,
theophylline, verapamil and warfarin.
H2 blockers can produce the following effects
during therapeutic use: cardiovascular (bradycardia, hypotension, AV block and
sinus arrest (especially with rapid IV administra- tion); haematologic
(agranulocytosis, pancytopenia, aplastic anaemia, and thrombocytopenia), and
dermatologic (including Stevens-Johnson syndrome, toxic epidermal necrolysis).
Cimetidine, ranitidine, and famotidine have been associated with drug-induced
fever, which typically resolves within 48 to 72 hours after discontinuation of
the drug. The most consistent adverse reaction reported with famotidine is a
severe, throb-headache, with an incidence of up to 4.7%. This has also been
reported for ranitidine. There are also case reports which suggest an
association between ranitidine use and hepatotox- icity. Gynaecomastia and increased
prolactin levels may be seen following therapeutic doses of cimetidine.
toxicity is rare with these compounds. There is one report of cimetidine
overdose producing tachycardia, mydriasis, and slurred speech. Other effects
reported include bradycardia, confusion, and vomiting. Bradycardia,
hypotension, and cardiac arrest may occur if cimetidine is given rapidly
intravenously. Cimetidine has caused complete atrioventricular block, wide-
complex tachycardia, and cardiac arrest after both oral and intravenous doses.
Sinus bradycardia is the most frequently reported cardiovascular effect. Dry
mouth, mild drowsiness, epigastric discomfort with diarrhoea, muscle pain,
headache, dizziness, delirium, psychosis, elevated liver or kidney func-tion
tests, leukopenia, and thrombocytopenia have also been reported. Visual
hallucinations, CNS depression, seizures, dystonia and coma have occurred.
administration can cause confusion, restlessness, extrapyramidal effects,
seizures, and peripheral neuropathies.
of acute toxicity involves administration of acti-vated charcoal, and
supportive measures. Convulsions can be controlled with benzodiazepines or
barbiturates. Bradycardia usually responds to atropine. Haemodialysis may be
useful. However, according to some investigators, less than 20% of a single
dose is recoverable in the dialysate of patients under- going haemodialysis.
it appears safe to manage most accidental ingestions at home, the maximum
tolerated dose has not been defined. Patients have survived ingestions of 12 to
24 grams. Ranitidine which is much more potent than cimetidine has also been
very rarely implicated in overdose. There is one case report of accidental
overdose in a 3 month old child producing a dystonic reaction. So far, there
are no documented fatalities following an acute oral overdose of cimetidine
alone or any of its related agents.