Are second generation antihistamines like certizine and loratadine non cns active?

[d1nach]

Ive heard that second generation antihistamines are nonsedating because they dont cross the blood brain barrier.

Is this true and is there any proof of this? Or is this just a assumption based on not feeling drowsy after.

 

[CFC]

Have a read here:

Affinity for the P-Glycoprotein Efflux Pump at the Blood-Brain Barrier May Explain the Lack of CNS Side-Effects of Modern Antihistamines

Abstract

First generation H1 receptor antagonists are often associated with adverse CNS effects such as sedation, whereas modem, second generation antihistamines are generally non-sedating. The difference in therapeutic profile is mainly due to the poor CNS penetration of the modern derivatives. Current explanations for the differential ability of classical and modern antihistamines to cross the blood-brain barrier (BBB), based on differences in lipophilicity or protein binding, are inadequate. We have tested the hypothesis that non-sedating antihistamines fail to enter the CNS due to recognition by the P-glycoprotein (Pgp) drug efflux pump expressed on the luminal surface of cerebral endothelial cells forming the BBB in vivo.

The ability of several sedating and non-sedating antihistamines to affect the uptake of the Pgp model substrate [3H]-colchicine was examined using the immortalised rat brain endothelial cell line, RBE4, an established in vitro model of the BBB expressing Pep. All second generation antihistamines tested, significantly increased net accumulation of [3H]-colchicine to a level similar to that caused by the Pgp inhibitor verapamil. By contrast, the first generation antihistamines showed no affinity for Pgp. The results indicate that differences in the ability of classical and modern antihistamines to interact with Pgp at the BBB may determine their CNS penetration and as a consequence the presence or absence of central side-effects.

http://www.tandfonline.com/doi/abs/10.3109/10611860108997930

And here:

Sedation and performance impairment of diphenhydramine and second-generation antihistamines: A meta-analysis

Abstract

Background: Antihistamines are among the most frequently used medications in the United States. Despite dramatically higher cost, second-generation antihistamines are replacing diphenhydramine because of the perception that they are not constrained by its sedating effects. Objective: We sought to examine, through meta-analytic procedures, the collective evidence regarding the sedating and performance-impairing effects of diphenhydramine relative to placebo and second-generation antihistamines. Methods: A search that began with the MEDLINE database was limited to those studies that included patients with atopic disease and control subjects, were blinded and randomized clinical trials, objectively examined alertness and psychomotor performance, reported means and variances, and were written in English. Information was systematically abstracted from the resulting 18 articles, and effect size was calculated. Results: Diphenhydramine impaired performance relative to placebo control and second-generation antihistamines, including acrivastine, astemizole, cetirizine, fexofenadine, loratadine, and terfenadine. However, results were quite varied, the average sedating effect of diphenhydramine was modest, and in some instances results of tests of performance in the diphenhydramine group showed less sedation than in the control or second-generation antihistamine groups. A significant (P < .05) average effect size indicated a mild sedating effect caused by second-generation antihistamines in comparison with placebo. Conclusion: The absence of a consistent finding of diphenhydramine-induced sedation is surprising given that most studies have been designed to increase the probability of this outcome, including administering a 50-mg dose. On the basis of this meta-analysis of performance-impairment trials, a clear and consistent distinction between sedating and nonsedating antihistamines does not exist.

http://www.sciencedirect.com/science/article/pii/S0091674903008704

 

[d1nach]

Very interesting thank you.

 

[Morpheus19]

They do cross the blood brain barrier, all that's needed is a bit of a higher dose.

With reference to the paper by Mann et al,1 the dichotomy between antihistamines of the first and second generation was introduced to indicate a big pharmacological difference between these drugs. The second generation antihistamines were less soluble in lipid and thus less readily penetrated the blood-brain barrier. When given to people in therapeutic doses, terfenadine produced about 17% occupancy of histamine H1 receptors in the frontal lobe whereas the first generation antihistamine chlorpheniramine produced about 77% occupancy.2 In rats receptor binding increases with the dose of several first and second generation antihistamines until full receptor saturation occurs.3 Thus the “non-sedating” title of the second generation antihistamines refers to a low tendency to diminish central arousal when taken in therapeutic doses. There is no reason to believe, however, that all non-sedating antihistamines have exactly the same low tendency to cross the blood- brain barrier. The study by Mann et al illustrates this point.1 Their prescription-event monitoring study showed that second generation antihistamines differ in their potential to produce sedation. The odds ratios for the incidence of sedation were 0.63 for fexofenadine, 2.79 for acrivastine, and 3.53 for cetirizine compared with loratadine.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1118461/

 

[d1nach]

Thank you! I thought i was going crazy i switched from equal dose dph for nausea to certizine and then loratadine and they all felt more or less similar . Do you know a more exact ratio of muscarinic acetylcholinergic antagonism for loratadine vs diphenhydramine ?

Thanks again That was a big help

 

[Morpheus19]

Thank you! I thought i was going crazy i switched from equal dose dph for nausea to certizine and then loratadine and they all felt more or less similar . Do you know a more exact ratio of muscarinic acetylcholinergic antagonism for loratadine vs diphenhydramine ?

Thanks again That was a big help

Just use certizine. It's the one with no anticholinergic activity, as it is highly selective for h1-antagonism: "Cetirizine did not bind at any of the receptors investigated, except H1 sites, even at concentrations as high as 10 mumol/L." https://www.ncbi.nlm.nih.gov/pubmed/1979798

So no increased risk of dementia (look up the studies).