Main unwanted side effect of sedating antihistamines

For example, in inflammation the p H of the tissues is reduced[, histamine receptors are situated on the cellular membranes of cells, including vascular and airways smooth muscle, mucous glands, and sensory nerves, all of which are surrounded by the extracellular fluid.

Many factors affect concentration of free drug in this compartment.

But perhaps their greatest drawback is their ability to cross the blood-brain barrier and interfere with histaminergic transmission.

main unwanted side effect of sedating antihistamines-23main unwanted side effect of sedating antihistamines-13

However, in chronic urticaria in which local histamine concentrations are high, the differences do seem to be important.

For example, in head to head studies in this condition levocetirizine appears significantly more effective than desloratadine[, which shows the inhibition of the histamine-induced flare response (indicative of the prevention by levocetirizine of sensory neurone stimulation in the extravascular space) plotted against the concentration of free drug in the plasma.

Second, they have unwanted side effects, particularly central nervous system and anti-cholinergic effects, and have the potential for causing severe toxic reactions which are not shared by second-generation H.

However, levocetirizine may cause somnolence in susceptible individuals while fexofenadine has a relatively short duration of action requiring twice daily administration for full all round daily protection.

In this study in children,[] plasma concentrations of drug are near maximum by 30 minutes and yet it takes an additional 1.5 hours for the drug to diffuse into the extravascular space to produce a maximal clinical effect. ] as the time for the wheal to be inhibited by at least 70%, is less prolonged, being 8.5 hours for 120 mg fexofenadine compared with 19 hours for cetirizine.

In adults, the maximal inhibition of the flare response is usually ~4 hours for levocetirizine, fexofenadine, and desloratadine[ Hysteresis loop of the inhibition of the histamine-induced flare response plotted against the plasma concentration of unbound levocetirizine after administration of a single 5-mg dose to children. The primary reason for the shorter duration of action of fexofenadine is that it is actively secreted into the intestine and urine[-antihistamines has focused on the histamine-dependent early phase symptoms of the allergic response, it is now becoming clear that these drugs have anti-inflammatory effects.Medicinal chemistry was very different in those days compared with the present day as elegantly described by Emanuel in his review entitled "Histamine and the antiallergic antihistamines: a history of their discoveries."[] The usual way of testing novel compounds was to measure histamine-induced contractions of pieces of muscle from experimental animals, usually guinea-pig intestine, suspended in an organ bath.Candidate antihistaminic compounds were primarily modifications of those synthesized as cholinergic antagonists and are from diverse chemical entities, ethanolamines, ethylene diamines, alkylamines, piperazines, piperidines, and phenothiazines.B, A surface view of an activated receptor with histamine linking domains III and V.C, A surface view of an inactive receptor with cetirizine linking domains IV and VI.Thus, the calculation of receptor occupancy after single oral doses of drug shows values of 95%, 90%, and 71% for fexofenadine, levocetirizine, and desloratadine, respectively, indicating that they are all very effective H-antihistamines.

Tags: , ,