18.5: Upper Respiratory Drugs: First and Second-Generation Antihistamines

Antihistamines are a class of drugs widely used to alleviate the symptoms of allergies, such as sneezing, itching, and nasal congestion. They work by inhibiting the actions of histamine, which is released by immune cells in response to allergenic substances or tissue injuries.

Histamine binds to specific receptor sites, known as H1 receptors, on tissue cells, triggering inflammation and swelling. Antihistamines combat these effects by competing with histamine for these receptor sites. By blocking the binding of histamine at H1-receptor sites, antihistamines effectively reduce inflammation and local tissue swelling, thereby relieving allergy symptoms.

Antihistamines can be divided into first-generation and second-generation agents based on their characteristics and side effect profiles. First-generation antihistamines, including diphenhydramine (Benadryl), chlorpheniramine (Chlor-Trimeton), and promethazine (Phenergan), block histamine at central and peripheral H1 receptors. They also exhibit anticholinergic effects by blocking muscarinic acetylcholine receptors in the peripheral nervous system. Because they can cross the blood-brain barrier into the central nervous system (CNS), they may cause CNS depression and induce drowsiness, which is often undesirable. They also block acetylcholine at neuronal and neuromuscular muscarinic receptors.

Second-generation antihistamines, on the other hand, are designed to selectively bind to peripheral H1 receptors. Examples of these drugs include cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra). Owing to their design, these drugs have reduced penetration into the CNS, resulting in less sedation than their first-generation counterparts.

Antihistamines are typically administered orally but can also be given via intravenous and intramuscular routes, depending on the drug and the patient's condition. While they are generally considered safe, antihistamines, particularly those of the first generation, may lead to CNS side effects such as fatigue, and dizziness, and anticholinergic side effects, such as dry mouth, blurred vision and urinary retention. It is essential to use these medications under a healthcare professional's guidance and report any adverse effects promptly.

Antihistamines relieve allergic symptoms by blocking the actions of histamine, a chemical released by the immune system in response to allergies or tissue injury.

They compete with histamines and block their binding at the histaminic H1-receptor sites, reducing inflammation and swelling of the local tissues.

Antihistamines can be classified into first-generation and second-generation agents.

First-generation drugs block histamines at central and peripheral H1 receptors and acetylcholine at neuronal and neuromuscular muscarinic receptors. They can also cross the blood-brain barrier into the central nervous system, leading to potential CNS depression and drowsiness.

In contrast, second-generation drugs selectively bind to peripheral H1 receptors. Because they are designed to have reduced CNS penetration, they result in less sedation.

Typically taken orally, antihistamines can also be administered via intravenous and intramuscular routes.

Although considered safe, certain antihistamines may lead to CNS side effects such as fatigue, dry mouth, and dizziness.