**Core Concept**
The question is testing the knowledge of long-acting antihistamines, which are a class of drugs used to treat allergic reactions by blocking the action of histamine on histamine receptors. These receptors are involved in the mediation of allergic responses, including vasodilation, increased vascular permeability, and smooth muscle contraction.

**Why the Correct Answer is Right**
The longest acting antihistaminic is **desloratadine**. It has a long duration of action due to its high lipophilicity, which allows it to bind to histamine receptors for a longer period. Desloratadine is a non-sedating antihistamine that selectively blocks the peripheral H1 receptors, thereby reducing the symptoms of allergic rhinitis and urticaria.

**Why Each Wrong Option is Incorrect**
* **Option A:** **Diphenhydramine** is a first-generation antihistamine with a relatively short duration of action and significant sedative effects, making it less suitable as a long-acting antihistaminic.
* **Option B:** **Cetirizine** is a second-generation antihistamine with a moderate duration of action, but it is not as long-acting as desloratadine.
* **Option C:** **Fexofenadine** is another second-generation antihistamine with a moderate duration of action, but it is not as long-acting as desloratadine.

**Clinical Pearl / High-Yield Fact**
Long-acting antihistamines like desloratadine are useful in managing chronic allergic conditions, as they provide sustained relief from symptoms without the sedative effects associated with first-generation antihistamines.

**Correct Answer: D. Desloratadine**