Z-Deen Mechanism of Action

Pharmacology: Pharmacodynamics: Loratadine is a second generation antihistamine with non-sedating properties. It is also a potent long-acting antihistamine with selective peripheral H₁ receptor antagonist activity. Prolonged nature of antihistaminic effect may result from the drug slow dissociation from the H₁ receptors or the formation of the active metabolite, desloratadine. The presence of a carboxyethyl ester moiety in Loratadine may limit distribution of the drug across the blood-brain barrier into the CNS. While the drug exhibits less affinity for histamine H₁ receptor in the CNS, with a resultant decreased potential for adverse CNS effects, such as drowsiness, compare with many other antihistamines. Loratadine has low affinity for cholinergic receptor therefore possesses less anticholinergic-like effect such as dryness of the nose, mouth, throat, or lips. During clinical studies of patients receiving Loratadine for weeks (2-24 weeks), decreased efficacy of inhibition of skin reactivity to allergen or histamine does not occur, as in the therapy of first generation antihistamines.
Pharmacokinetics: Absorption: Following oral administration, Loratadine is rapidly absorbed from the GI tract. Antihistaminic effect appears within 1-4 hours. Peak effect results within 8-12 hours. The effect persists for 24 hours or longer. Food may increase bioavailability and delay time-to-peak plasma concentration of the drug and metabolite by about 1 hour.
Distribution: Loratadine is highly bound (97% to 99%) and its active major metabolite desloratadine moderately bound (73% to 77%) to plasma proteins. Loratadine and its active metabolites are distributed into breast milk. Non significant amount of the drug appears to cross the blood-brain barrier.
Metabolism: Loratadine is metabolized in the liver by the cytochrome P-450 (CYP) microsomal enzyme system, mediated principally by CYP3A4 and to a lesser extent by CYP2D6. In the presence of a CYP3A4 inhibitor, Loratadine is principally metabolized to desloratadine by the CYP2D6 isoenzyme. In patients with hepatic impairment, the half-life of Loratadine and desloratadine may be prolonged.
Elimination: The elimination half-life of Loratadine and desloratadine are 8.4 and 28 hours, respectively. 40% of Loratadine is excreted into the urine and 40% in the feces, mostly metabolites.