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Histamine is a biologically active amine key to allergic inflammation and gastric acid secretion, and it also functions as a neurotransmitter. The primary focus of the text is on the action of antihistamines on the H1 receptor, situated on vascular endothelial cells, bronchial airways, and within the brain. Histamine is typically contained within the granules of mast cells and basophils. When these cells get exposed to the appropriate antigens, they burst open to release histamine. Allergic inflammation happens due to the action of histamine on the H1 histamine receptor.

H1 receptors are connected with a G sub q protein, while H2 receptors couple to a G sub s protein, resulting in an increase in cAMP. H1 receptor activation causes increased nasal and bronchial mucus production, pain, pruritus, vasodilation, and increased vascular permeability, resulting in hives. Antihistamines specifically block H1 receptors, making them useful for treating allergies. Note that, first-generation antihistamines, due to their lipophilic nature, can easily cross the blood-brain barrier, making them effective against motion sickness and insomnia, but could result in severe cognitive impairment and delirium in elderly patients. In contrast, second-generation antihistamines, such as fexofenadine, cetirizine, and loratadine demonstrate lesser incidence of side effects, due to their less lipophilic nature, which prevents them from crossing the blood-brain barrier.

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How is histamine linked to allergic reactions?

Histamine is stored within the granules of mast cells and is released during allergic reactions. Once released, it interacts with H1 and H2 histamine receptors, mediating various allergic responses. The activation of the H1 receptor, coupled to the Gq protein, induces allergic inflammation by increasing vascular permeability, bronchial mucus production, and causing constriction of bronchial smooth muscle. Moreover, the H1 receptor regulates sleep and arousal, as histamine also functions as a neurotransmitter.

What role do antihistamines play in managing allergic symptoms?

Antihistamines, specifically H1 receptor blockers, treat allergic symptoms by neutralizing the effects of histamine. This is particularly beneficial for conditions like hives and allergic rhinitis, where H1 receptor blockers are considered first-line therapy. Histamine's actions on the H2 receptor, which is coupled to the Gs protein, lead to gastric acid secretion. By blocking these effects, pertinent antihistamines can help manage related conditions.

Which conditions are primarily treated using 1st-generation H1 receptor blockers?

First-generation H1 receptor blockers like diphenhydramine, dimenhydrinate, chlorpheniramine, hydroxyzine, meclizine, and promethazine are particularly effective against vestibular nausea, motion sickness, and allergies. Their lipophilic nature enables them to enter the CNS and act on the vestibular system and brainstem, often causing drowsiness. Additionally, they can manage extrapyramidal side effects triggered by antipsychotics, as their antimuscarinic properties help re-establish the dopaminergic-cholinergic balance. They are also known to stimulate appetite and weight gain due to their anti-serotonergic effects.

What side effects are associated with 1st-generation H1 receptor blockers?

Being lipophilic, these drugs easily cross the blood-brain barrier leading to central effects such as drowsiness. Their ability to antagonize peripheral and central muscarinic, serotonin, and alpha-1 receptors can result in a variety of side effects, including pupillary dilation, dry mouth, urinary retention, constipation, exacerbation of glaucoma, delirium, dizziness, hypotension, and cognitive impairment, especially in the elderly.

How do 2nd-generation H1 receptor blockers differ from the 1st-generation?

Second-generation H1-blockers like fexofenadine, cetirizine, and loratadine are chemically designed to be less lipophilic. This makes them less likely to cross the blood-brain barrier, resulting in fewer sedative effects. Moreover, they exhibit diminished antimuscarinic, antiserotonergic, and anti-alpha adrenergic properties, reducing the scope of potential side effects compared to the 1st-generation.