Antihistamines are medications that can be used for a variety of conditions, such as alleviating symptoms of a common cold, to decrease motion sickness, and they can occasionally be used to help induce sleep.
But the primary use of antihistamines is to alleviate symptoms of allergic conditions, such as allergic rhinitis, allergic conjunctivitis, and urticaria, as well as as an adjunctive therapy for anaphylaxis, which is a severe systemic allergic reaction.
Now, these allergic conditions are usually triggered by an environmental factor, like pollen, which causes mast cells to release inflammatory mediators like histamine, triggering a widespread response.
When acting on the brain, histamine promotes wakefulness. In the bronchi, histamine causes smooth muscle contraction, leading to bronchoconstriction, while in blood vessels, it causes smooth muscle relaxation, resulting in vasodilation.
In addition, histamine increases vascular permeability, allowing fluid to accumulate in the airways, which increases nasal and bronchial secretions.
Now, antihistamines can be administered orally, topically, and injected intravenously or intramuscularly.
Once administered, they block the histamine H1 receptors, preventing histamine from binding and triggering its effects on target organs.
There are two main groups of antihistamines: first generation antihistamines include chlorpheniramine, diphenhydramine, hydroxyzine and promethazine, while second generation antihistamines include loratadine, fexofenadine, cetirizine, and levocetirizine.
Now, peripherally, both generations of antihistamines can block H1 receptors in the bronchi, resulting in bronchodilation, which improves airflow, while in the blood vessels of the skin, they cause smooth muscle contraction, which leads to vasoconstriction, in turn decreasing localized flushing; in the capillaries, they decrease vascular permeability, reducing edema; in mucous membranes, they reduce nasal and bronchial secretions; and in peripheral nerves, they reduce the sensation of itching.
Now, one important feature that is unique to first generation antihistamines is that they can more easily cross the blood brain barrier, meaning that they can also block H1 receptors in the brain, which can cause sedation. For this reason, second generation antihistamines are better suited for use during the day.
First generation antihistamines are also more commonly associated with side effects, since they can block other types of receptors.
Blockade of muscarinic receptors results in anticholinergic side effects, such as dry mouth, blurred vision, urinary retention and constipation, while blockade of alpha-1 adrenergic receptors may cause orthostatic hypotension.
Some antihistamines can also cause QT interval prolongation, which may predispose some clients to arrhythmias. Other side effects include irritability, confusion, hearing problems like tinnitus and wheezing.
As for contraindications, some first generation antihistamines are contraindicated during pregnancy, breastfeeding and in newborns; if needed, second generation antihistamines are preferred.
In addition, first generation antihistamines should generally be avoided in clients with narrow-angle glaucoma, arrhythmias, and in those who take other medications that prolong the QT interval, such as erythromycin and amitriptyline.
Also, due to their sedative effect, first generation antihistamines should be avoided in older clients because they increase their risk of falls, as well as in clients who take other medications or substances that impair their mental status, such as alcohol, barbiturates, opioids and hypnotics.
In addition, first generation antihistamines are contraindicated in clients with benign prostatic hyperplasia, as they decrease urinary bladder contraction, which might cause urinary retention.
Promethazine, in particular, has a boxed warning for use in clients under 2 years of age, as it may lead to respiratory depression; as well as for severe tissue injury when used intravenously, since it is a vesicant.
Finally, second generation antihistamines should be used cautiously in clients with renal or hepatic disease.
