Mechanism of Action
Loratadine acts during the effector phase of an allergic reaction. It acts as a competitive antagonist of histamine and selectively blocks $H_1$-histamine receptors.
Unlike some other agents, the drug has high selectivity and does not affect other receptor subtypes (such as $H_2$-receptors, which are responsible for the gastric acid secretion or the vascular permeability components of Lewis's triple response).
By binding to $H_1$-receptors, loratadine prevents the initiation of the intracellular calcium cascade, which blocks smooth muscle contraction and the development of other histamine-mediated reactions.
Pharmacokinetics and Metabolism
The drug is administered enterally (orally). A crucial characteristic of loratadine as a second-generation antihistamine is that it virtually does not cross the blood-brain barrier (BBB). This is due to two factors:
- Low lipophilicity of the molecule.
- Active efflux of the drug from the BBB endothelium back into the bloodstream by the transport pump protein, P-glycoprotein.
Loratadine is a prodrug. Upon reaching the liver, it is metabolized by the cytochrome P450 isoenzyme CYP3A4. This yields the active metabolite, desloratadine. This biotransformation provides the prolonged duration of the drug's effect, which ranges from 12 to 24 hours.
Pharmacological Effects and Indications
The drug affects immune processes and suppresses inflammation. In terms of antihistamine potency, loratadine demonstrates a moderate effect (inferior to first-generation agents such as promethazine and clemastine).
Due to its long duration of action, it is convenient to use—prescribed only once daily. In pediatric practice, loratadine is considered one of the drugs of choice for treating allergies in children.
Side Effects and Drug Interactions
Because loratadine does not penetrate the central nervous system, it lacks the pronounced sedative effect characteristic of first-generation agents (e.g., diphenhydramine). Furthermore, it possesses no anticholinergic (atropine-like) or antiemetic activity.
The main clinical challenge lies in drug-hepatic interactions. Because metabolism occurs via CYP3A4, concurrent administration of inhibitors of this enzyme (such as ketoconazole, erythromycin, and grapefruit juice) slows down the breakdown of loratadine. This leads to increased blood concentrations and a heightened risk of adverse reactions.
Clinical Administration
The drug is available in 10 mg tablets. It is administered orally before meals, one tablet once daily.