Sunday's family reunion: H2-receptor antagonists
Welcome to a new weekly series. I chose this title because, generally, families gather on Sundays to have lunch together. The families I will talk about here, in particular, are classes of molecules.
Molecules will be described only from a pharmacological point of view. Nevertheless, chemistry may "drop in" every so often, in particular, to explain awesome mechanisms.
Moreover, I hope usual readers of KinasePro will find this interesting, even if new drugs won't be very common.
Today, we start with an old and quite small class: H2-antagonists. I said old and small, but this doesn't mean unimportant by any means.
Before the introduction of PPIs (proton pump inhibitors), these drugs were of paramount important. Nowadays, due to their cost, they are still prescribed for treating gastroesophageal reflux, peptic ulcer and stress-related gastritis (we don't live peaceful lives, do we?).
Four drugs are currently in clinical use: cimetidine, ranitidine, famotidine and nizatidine. They are amazingly selective for histamine type 2 receptors.
H2 receptors are situated on parietal cells of the stomach, those which secrete HCl in the lumen. The interaction between histamine and said receptor activates adenylyl cyclase. This inceases the intracellular level of c-AMP, which stimulates the pump regulating the secretion of H+ ions.
Basically these antagonists reduce by 60-70% the daily secretion of hydrochloric acid. In particular, these drugs have terrific efficiency on nocturnal secretion (better than newer PPIs).
Still, there are more drawbacks here than with PPIs, which have almost no adverse effect. However, considering the average number and frequency, these drugs are extremely safe. Sure, they might induce diarrhea, myalgias and constipation, but these are annoyingly common.
More interestingly, when administered intravenously, confusion may occur.
Cimetidine, the oldest, is also the least selective, messing up the metabolism of androgens, estradiol and prolactin. So, long therapies at quite high doses can end up with pretty nasty stuff such as gynecomastia in men and galactorrhea in women.
Cimetidine triggers metabolic inhibition of c-P450s too.
