Histamine receptor antagonists interactions

As we move forward with our discussion, we ll devote a section of this chapter to each of the key neurotransmitter systems that psychotropic medications interact with. We will discuss the following systems norepinephrine, dopamine, serotonin, GABA, acetylcholine, and histamine. Within each of the sections is a description of the effects that can be anticipated when a medication enhances the activity of that transmitter (reuptake inhibitors or agonists), and the effects to expect when a medication interferes (receptor antagonists) with the activity of that same transmitter. We will then describe strategies that can be implemented to help minimize and/or manage these side effects. 

H2-antagonists competitively interact with the H2-receptor. They are very specific for the H2-sub-type of the histamine receptor. 

Histamine H3 receptor stimulation is not involved in the direct effects of histamine in the permeability response in in vivo rats, (Pile and Smaje., 1992) In this last study, Hi and H2 receptors seem to have a dominant role. However, the H3-receptor antagonist thioperamide prevents the effects induced by histamine and by the Hi-agonist 2-thiazolylethylamine, thus suggesting non-specific interactions of these histamine receptor ligands... 

Interactions. Drugs that lower gastric acidity, e.g. antacids, histamine H2 receptor antagonists, impair the absorption of ketoconazole from the gastrointestinal tract. Like all imidazoles, ketoconazole binds strongly to several cytochrome P450 isoenzymes and thus inhibits the metabolism (and increases effects of) oral anticoagulants, phenytoin and cyclosporin, and increases the risk of cardiac arrhythmias with terfenadine. A disulfiram-like reaction occurs with alcohol. Concurrent use of rifampicin, by enzyme induction of CYP 3A, markedly reduces the plasma concentration of ketoconazole. 

The metabolism of lorazepam (e.g., Ativan), oxazepam (e.g., Serax), and temazepam (e.g., Restoril) are not likely to be affected, and one of these agents may be preferred when a benzodiazepine is indicated in a patient being treated with cimetidine. The experience with ranitidine (e.g., Zantac), famotidine (Pepcid), and nizatidine (Axid) suggests that these agents are not likely to inhibit hepatic enzyme systems, and these other histamine H2-receptor antagonists are less likely than cimetidine to interact with other drugs that are metabolized via these pathways. 

The available data on a possible interaction between histamine H2 receptor antagonists and ciclosporin are inconclusive. Whereas neither cimetidine nor ranitidine significantly altered ciclosporin pharmacokinetics, there was an increase in serum creatinine concentration in patients taking both ciclosporin and cimetidine, but not ranitidine. The clinical significance of this interaction is probably limited, and it has been attributed to competition of cimetidine with creatinine for tubular secretion (251). 

Nizatidine is a histamine H2 receptor antagonist. Experience with it is still too hmited to make valid comparisons with its earher congeners. Data sheet warnings of possible adverse effects refer to skin rash, nrticaria, somnolence, and thrombocytopenia. Nizatidine is said not to give problems with drug interactions or to affect androgen status. 

Martinez-Mlr, M.I. etal. (1990) Three histamine receptors Hi, H and Hj visualised In the brain of human and non-human primates. Brain Res., 528, 322-327. Leurs, R. et al. (1995) Evaluation of the receptor selectivity of the H3 receptor antagonists, iodophenprc it and thioperamide An interaction with the 5-HT receptor revealed. Br. J. Pharmacol.. 116, 2315-2321. 

Single-dose interaction studies have demonstrated that concurrent administration of tolterodine LA with antacid leads to a rapid release of drug (70% within 4 hours) and results in a 1.5-fold elevation in tolterodine peak plasma concentration compared with placebo. The clinical implications of this interaction and whether a similar interaction exists with gastric acid suppressants such as the histamine H2 -receptor antagonists and proton pump inhibitors are unclear. In the same study, the pharmacokinetics of oxybutynin XL were unaltered by antacid administration. ... 

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